Diseases of Laboratory Primates





                     PAT 707, Diseases of Laboratory Animals II

                               Part 1: Viral Diseases



                            Prepared by Trenton R. Schoeb















                         Department of Comparative Medicine
                         University of Alabama at Birmingham





                               Winter Quarter 1989-90Herpesvirus simiae

1.  Historical:

      Originally reported in 1934 by Sabin and Wright, who isolated it from a man who
died after being bitten by a rhesus monkey.

2.  Agent:

      An alpha herpesvirus (same group as Herpesvirus hominis); syn. Herpes B. 
Antigenically similar to HSV-1, HSV-2, and SA-8.

3.  Epizootiology:

      Macaques (especially rhesus) are natural hosts.  Other species are
experimentally susceptible.  Transmission among monkeys by contact, fomites, aerosol;
to man by bites, infected cells or tissues, aerosol.  (Transmission to humans by
exposure to monkey saliva via bites or scratches has not been consistently
documented, however.)  Probably monkeys are infected for life and a high proportion,
if not 100%, of adult individuals in infected colonies harbor virus.

      Through 1987, 22 human cases were reported.  (A few other cases are attributed
to B virus infection, but lack adequate documentation.)

4.  Clinical:

      In monkeys, lingual and labial vesicles which rupture leaving ulcers that heal
in 1-2 weeks; conjunctival and cutaneous lesions in a few cases.  Infection probably
also occurs without lesions in many cases.  In man, local erythema and vesiculation
at site of inoculation, localized neurologic symptoms, fever, regional
lymphadenopathy, muscular aches, CNS signs (mostly paralytic), die in coma of
respiratory failure within a few days to a few weeks.
      Twenty of the 22 human patients developed encephalitis.  Fifteen of these died. 
Two of the Pensacola patients had mild disease; they were treated with acyclovir but
its efficacy for treating human infections has not been established.  The frequency
of mild or symptomatic human infections is not known.

5.  Pathology:

      Microscopic lesions in man and monkeys are similar. "Ballooning" degeneration,
multinucleation, and necrosis of epithelial and other affected cells and characteristic
nuclear inclusions.  In man, multifocal necrotizing encephalomyelitis and multifocal
necrosis in spleen, liver, lymph nodes, and adrenals.  A similar disseminated disease
occurs rarely in rhesus and occasionally in cynomolgus monkeys.

6.  Diagnosis:

      Signs, lesions, virus isolation, rabbit inoculation.  Serologic tests including
ELISA and serum neutralization also can be used; however, results of the usual tests
can be complicated by antibodies to human herpes simplex virus and to SA-8 virus. 
(Competition ELISA can be used to distinguish, if necessary.)  Furthermore, it is not
certain that infected monkeys always have diagnostic titers.

7.  Control:

      The CDC recommends that macaques be used for research only when necessary,
and that, if possible, those used should be free of the virus and housed so as to
prevent infection.  Macaques should be handled only with adequate physical or
chemical restraint, and handlers should wear protective clothing, gloves, and masks. 
The CDC does not recommend routine screening because the reliability of negative
results has not been ascertained and because handling the monkeys increases the
risk of human exposure.  Monkeys with oral lesions suggestive of active infection
should be quarantined.  Handlers and investigators should be educated concerning
the risks of exposure to B virus and the need for proper protective measures,
immediate reporting and treatment of injuries received while handling monkeys, and
obatining immediate medical attention for any condition suggestive of B virus
infection.

      Limited experimental and clinical data indicate acyclovir to be the drug of choice
for treatment.  For consultation concerning diagnosis and treatment, one can contact
the Viral Exanthems and Herpesvirus Branch, CDC, 404-329-1338, or the Southwest
Foundation for Biomedical Research, 512-674-1410.

8.  References:

Balfour HH Jr. 1984. Acyclovir and other chemotherapy for herpes group viral
infections. Ann Rev Med 35:27-291.

Boulter EA et al. 1980. Successful treatment of B virus (Herpesvirus simiae) infection
with acyclovir. Br Med J 280:681-683.

Boulter EA et al. 1982. A comparison of neutralization tests for the detection of
antibodies to Herpesvirus simiae (Monkey B virus) Lab Anim Sci 32:150-152.

Bryan BL et al. 1975. Recovery from encephalomyelitis caused by Herpesvirus simiae.
Arch Intern Med 135:868-870.

Cabasso VJ et al. 1967. Correlation of B virus and herpes simplex virus antibodies in
human sera. J Lab Clin Med 70:170-178.

Centers for Disease Control. 1973. Herpes B encephalitis--California. Morbity and
Mortality Weekly Report 22:333-334.

Centers for Disease Control. 1987. B-virus infection in humans--Pensacola, Florida.
Morbidity and Mortality Weekly Report 36:289-290.

Centers for Disease Control. 1987. Guidelines for prevention of Herpesvirus simiae (B
virus) infection in monkey handlers. Morbidity and Mortality Weekly Report 36:680-
689.

DiGiacomo RF. 1988. Guidelines for prevention of herpesvirus simiae (B-virus)
infection in monkey handlers [letter] Lab Anim Sci 38:558.

Hartley EG. 1964. Naturally occurring B virus infection in cynomolgus monkeys. Vet
Rec 76:555-557.

Heberling RL, Kalter SS. 1987. A dot-immunobinding assay on nitrocellulose with
psoralen inactivated Herpesvirus simiae (B virus). Lab Anim Sci 37:304-308.

Hilliard JK et al. 1987. Herpesvirus simiae (B-virus): Replication of the virus and
identification of viral polypeptides in infected cells. Arch Virol 93:185-198.

Hilliard JK et al. 1986. Rapid identification of Herpesvirus simiae (B virus) DNA from
clinical isolates in nonhuman primate colonies. J Virol Methods 13:55-62.

Hull RN. 1971. B virus vaccine. Lab Anim Sci 21:1068-1071.

Hummeler K et al. 1959. Encepahalomyelitis due to infection with Herpesvirus simiae
(herpes B virus): a report of two fatal acquired cases. New Engl J Med 261:64-68.

Juel-Jensen BE. 1982. Postexposure immunoprophylaxis against B virus infection. Brit
Med J 284:113-114.

Kaplan JE et al. 1987. Guidelines for prevention of Herpesvirus simiae (B-virus)
infection in monkey handlers (letter). Lab Anim Sci 37:709-712.

Kaplan JE. 1988. Herpesvirus simiae (B virus) infection in monkey handlers [letter]
J Infect Dis 157:1090.

Keeble SA. 1960. B virus infection in monkeys. Ann NY Acad Sci 85:960-969.

Loomis MR et al. 1981. Fatal herpesvirus infection in patas monkeys and a black and
white colobus monkey.  J Am Vet Med Assoc 179:1236-1239.

McClure HM et al. 1973. Disseminated herpesvirus infection in a rhesus monkey
(Macaca mulatta).  J Med Primatol 2:190-194.

Palmer AE. 1987. B virus, Herpesvirus simiae: Historical perspective. J Med Primatol
16:99-130.

Sabin AB, Wright AM. 1934. Acute ascending myelitis following a monkey bite with the
isolation of a virus capable of reproducing the disease. J Exp Med 59:115-136.

Van Hoosier GL Jr, Melnick JL. 1961. Neutralizing antibodies in human sera to
Herpesvirus simiae. Texas Rep Biol Med 19:376-380.

Vizoso AD. 1975. Recovery of Herpesvirus simiae (B virus) from both primary and
latent infections in rhesus monkeys. Brit J Exp Pathol 56:485-488.

Zwartouw HT et al. 1984. Transmission of B virus infection between monkeys especially
in relation to breeding colonies. Lab Animal 18:125-130.


                                Herpesvirus tamarinus

1.  Agent:

      Syn. Herpes T, Herpesvirus saimiri type 1

2.    Epizootiology:

      Natural host (life-long latent infection with periodic shedding) is squirrel
monkey, perhaps also Cebus and Ateles spp. (serologic evidence).  Severe disease in
marmosets and owl monkeys.  Transmission by contact, fomites, aerosol.

3.    Clinical:

      In squirrel monkeys: usually none, but in acute disease can have lip, tongue,
palate ulcers.  Systemic disease and death not reported.  In owl monkeys and
marmosets, rapidly spreading epizootics with high morbidity and mortality (up to
100%), characterized by oral and cutaneous vesicles and ulcers, conjunctivitis, and
occasionally, apparent hyperesthesia or paresthesia indicated by intensive
scratching.

4.  Pathology:

      Focal necrosis with giant cells and inclusions in skin, oral mucosa,
gastrointestinal tract, lymph nodes, adrenals, and liver, and in some cases,
encephalitis.  (Microscopic lesions in the cases in our files do not contain giant cells.)

5.  Diagnosis:

      Signs and lesions, virus isolation and identification.

6.  Control:

      House reservoir and susceptible primates separately.
7.    References:

Desrosiers RC 1981. Herpesvirus tamarinus and its relation to Herpes simplex virus.
J Gen Virol 56:119-130.

Emmons RW et al. 1969. Natural fatal infection of an owl monkey with herpes-T virus.
J Infect Dis 118:153-159.

Hunt RD, Melendez LV. 1966. Spontaneous herpes-T infection in the owl monkey (Aotus
trivirgatus).  Path Vet 3:1-26.

Morita M. 1981. Fatal Herpesvirus tamarinus infection in cotton-topped marmosets
(Saguinus oedipus).  Jap J Med Sci Biol 34:268-270.

Sauer GM, Bishop W. 1963. Inclusion body hepatitis in marmosets. Lab Anim Care
13:790-792.


                                 Herpesvirus hominis

1.    Agent:

      Herpesvirus hominis type 1 (herpes simplex) and type 2 (genital herpes).

2.  Epizootiology:

      Man is the natural host; most people are infected.  Generalized disease reported
in owl monkeys, gibbons, tree shrews, and gorilla.  Serologic evidence (ELISA +
immunoblotting) indicates that HSV-1 infections are common in gorillas and gibbons. 
Marmosets and Cebus spp. are susceptible experimentally.  Genital infections (HSV-2)
have been reported in chimpanzees.

3.  Clinical:

      In man, acute infection (usually in children less than 3 years old) produces
vesicular gingivostomatitis.  Recurrent exacerbations are characterized by vesicles
and ulcers on the lips ("fever blisters").  Owl monkeys: high morbidity and mortality,
conjunctivitis, nasal discharge, lethargy, course 4-7 days.  Gibbons: oral ulcers; some
develop CNS signs and die.  Tree shrews: emaciation, conjunctivitis, some die. 
Generalized disease in a gorilla also has been reported.  Genital herpes in chimps:
localized herpetic ulcers.

4.    Pathology:

      Morphologically indistinguishable from Herpesvirus tamarinus in owl monkeys,
although encephalitis occurs in more cases.  Gibbons: necrotizing
meningoencephalitis, inclusions.  Tree shrews: multifocal necrotizing and hemorrhagic
hepatitis and adrenal adenitis with inclusions.

5.    Diagnosis:

      Signs and lesions, virus isolation and identification.

6.    Control:

      Persons with active herpetic infection must stay away from susceptible
nonhuman primates.

7.    References:

Eberle R, Hilliard JK. 1989. Serological evidence for variation in the incidence of
herpesvirus infections in different species of apes. J Clin Microbiol 27:1357-1366.

Emmons RW, Lennette EH. 1970. Natural Herpesvirus hominis infection of a gibbon
(Hylobates lar).  Arch Ges Virusforsch 31:215-218.

Heldstab A et al. 1981. Spontaneous generalized Herpesvirus hominis infection of a
lowland gorilla (Gorilla gorilla gorilla).  J Med Primatol 10:129-135.

Kalter SS et al. 1972. Experimental Herpesvirus hominis type 2 infection in non-human
primates. Proc Soc Exp Biol Med 139:964-968.

Katzen S et al. 1971. Experimental Herpesvirus simplex infection in the owl monkey.
Proc Soc Exp Biol Med 125:391-398.

London WT et al. 1971. Genital Herpesvirus hominis type 2 infection of monkeys.
Obstet Gynecol 35:501-509.

McClure HM et al. 1972. Natural Herpesvirus hominis infection of tree shrews (Tupaia
glis).  Lab Anim Sci 22:517-521.

McClure HM et al. 1980. Natural genital Herpesvirus hominis infection in chimpanzees
(Pan troglodytes and Pan paniscus).  Lab Anim Sci 30:895-901.

Melendez LV et al. 1969. Natural Herpesvirus simplex infection in the owl monkey
(Aotus trivirgatus). Lab Anim Care 19:38-45.

Ramsey E et al. 1982. Fatal Herpesvirus hominis encephalitis in a white handed
gibbon.  J Am Vet Med Assoc 181:1429-1430.

Smith PC et al. 1969. The gibbon (Hylobates lar): A new primate host for herpes virus
hominis. I. A natural epizootic in a laboratory colony. J Infect Dis 120:292-297.


                                  Simian Varicella

1.    Agent:

      (i) Delta herpesvirus (DHV, Syn. Patas monkey herpesvirus).  First isolated in
1968 at Delta Regional Primate Research Center from patas monkeys.
      (ii) Liverpool vervet monkey herpesvirus (LVMHV).
      (iii) Medical Lake macaque herpesvirus (MLMHV).
      These viruses are very similar, if not identical, and are closely related to human
varicella-zoster virus.

2.    Epizootiology:

      Natural host of DHV is unknown.  Most natural cases have been in patas
monkeys, but disease in this species tends to feature high morbidity and mortality,
which is more characteristic of herpesviral infection in aberrant or
immunosuppressed hosts. African green monkeys and pigtailed macaques also are
susceptible.  LVMHV affects patas and African green monkeys; MLMHV, pigtailed,
Japanese, and cynomolgus macaques.  There has been a case of a varicella-like
disease in a young chimp at the Yerkes center, but the virus was lost in culture and
thus could not be identified.

3.    Clinical:

      Cutaneous rash with vesicles, oral vesicles and ulcers, high mortality.  MLMHV:
lower mortality, often self-limiting exanthematous disease.

4.    Pathology:

      Hyperplasia, "ballooning" degeneration, necrosis, blood-filled vesicles and
ulceration in stratified squamous epithelium; multifocal to diffuse necrosis in most
viscera, especially lung, liver, and lymphoid organs (may also be in digestive tract
and aderenals); widespread necrotizing vasculitis; inclusions in epithelium,
endothelium, and vascular smooth muscle of affected organs.

5.    Diagnosis:

      Signs, lesions, virus isolation.  Clinically and pathologically resembles
generalized varicella in immunosuppressed human hosts.

6.    Control:

      Uncertain--don't mix primate species.

7.    References:

Allen WP et al. 1974. Recent studies on the isolation and characterization of Delta
herpesvirus. Lab Anim Sci 24:222-228.

Ayers JP. 1971. Studies of the Delta herpesvirus isolated from the patas monkey
(Erythrocebus patas). Lab Anim Sci 21:685-695.

Blakely GA et al. 1973. A varicella-like disease in macaque monkeys.  J Infect Dis
127:617-625.

Clarkson MJ et al. 1967. A virus disease of captive vervet monkeys (Cercopithecus
aethiops) caused by a new herpesvirus.  Arch Ges Virusforsch 22:219-234.

Felsenfeld A, Schmidt NJ. 1975. Immunological relationship between Delta herpesvirus
of patas monkeys and varicella zoster virus of humans. Infect Immun 12:261-266.

Eppstein DA et al. 1989. Liposomal interferon-beta: sustained release treatment of
simian varicella virus infection in monkeys. J Infect Dis 159:616-620.

Felsenfeld A, Schmidt WJ. 1979. Varicella zoster virus immunizes patas monkeys
against varicella-like disease. J Gen Virol 42:171-178.

Gard EA et al. 1983. Disseminated intravascular coagulation secondary to simian
varicella in the patas monkey (Abstract). Lab Anim Sci 33:481.

Gard EA. 1982. Symptomatology and pathology of delta herpesvirus infection in a
patas monkey colony (Abstract). Lab Anim Sci 32:427-428.

Harbour A. 1979. The serological relationship of varicella zoster virus to other primate
herpesviruses. J Gen Virol 45:469-477.

Heuschele WP. 1970. Varicella (chicken pox) in three young anthropoid apes. J Am Vet
Med Assoc 136:256-257.

Lehner NM et al. 1984. Simian varicella infection in the African green monkey
(Cercopithecus aethiops).  Lab Anim Sci 34:281-285.

McCarthy K et al. 1968. Exanthematous disease in patas monkeys caused by herpes
virus.  Lancet 2:856-857.

Padovan D, Cantrell CA. 1986. Varicella-like herpesvirus infections of nonhuman
primates. Lab Anim Sci 36:7-13.

Roberts E et al. 1984. Pathologic changes of experimental simian varicella (Delta
herpesvirus) infection in African green monkeys (Cercopithecus aethiops).  Am J Vet
Res 45:523-530.

Schmidt NJ et al. 1983. Serological investigation of an outbreak of simian varicella in
Erythrocebus patas monkeys.  J Clin Microbiol 18:901-904.

Seibold HR, Allen WP. Varicella, Model No. 69. In Handbook of Animal Models of Human
Disease. Fasc. 5, Ed TC Jones, DB Hackel and G Migaki. Registry of Comparative
Pathology, AFIP, Washington DC, 1976.

Soike KF, Baskin GB. Varicella, Model No. 69, Supplemental update. In Handbook:
Animal Models of Human Disease, Fasc 12. Ed CC Capen, DB Hackel, TC Jones, and G
Migaki. Registry of Comparative Pathology, AFIP, Washington DC, 1983.

Soike KF et al. 1989. Enhancement of simian varicella virus infection in African green
monkeys by recombinant human tumor necrosis factor alpha. J Infect Dis 159:331-335.

Wenner HA et al. 1977. Clinical and pathogenetic studies of Medical Lake macaque
virus infection in cynomolgus monkeys (simian varicella).  J Infect Dis 135:611-622.

White RO et al. 1972. Chicken pox in young anthropoid apes. Clinical and laboratory
findings. J Am Vet Med Assoc 161-690-692.

Wolf RH et al. 1974. Pathology and clinical history of Delta herpesvirus infection in
patas monkeys.  Lab Anim Sci 24:218-221.


                                 Other Herpesviruses

1.    Oncogenic herpesviruses.

      (i) Herpesvirus saimiri (H. saimiri type 2): A latent virus of squirrel monkeys--
no disease.  Can cause malignant lymphoma after inoculation in marmosets, owl
monkeys, and spider monkeys, and in naturally infected owl monkeys.  Limited
serologic data and infection of some human cell lines in vitro with transformation
suggest that human infections are possible, but degree of hazard is unknown.

Ablashi V et al. 1971. Malignant lymphoma with lymphocytic leukemia induced in owl
monkeys by Herpesvirus saimiri. J Natl Cancer Inst 47:837-855.

Ablashi DV et al. 1988. Detection of antibodies to Herpesvirus saimiri late antigens in
human sera. Intervirology 29:217-226.

Cicmanek JL et al. 1974. Lymphoma in owl monkeys (Aotus trivirgatus) inoculated with
Herpesvirus saimiri: Clinical, hematologic, and pathologic findings.  J Med Primatol
3:8-17.

Daniel M et al. 1970. Malignant lymphoma induced in rabbits by Herpesvirus saimiri
(Abstr.) Bact Proc p. 195.

Desrosiers RC et al. 1985. A region of the Herpesvirus saimiri genome required for
oncogenicity. Science 228:184-187.

Desrosiers RC et al. 1986. Nononcogenic deletion mutants of Herpesvirus saimiri are
defective for in vitro immortalization. J Virol 57:701-705.

Desrosiers RC, Falk LA. 1982. Herpesvirus saimiri strain variability. J Virol 43:352-356.
Epstein MA. 1972. Burkitt's lymphoma and Herpesvirus saimiri lymphoma: Comparative
aspects. J Natl Cancer Inst 49:213-216.

Falk L, Wright T, Deinhardt F. 1976. Experimental infection of squirrel and marmoset
monkeys with attenuated Herpesvirus saimiri.  Cancer Res 36:707-710.

Giddens WE. 1978. Studies of cultured lymphocytes of the owl monkey (Aotus
trivirgatus) infected with Herpesvirus saimiri.  Lab Anim Sci 26:1113-1126.

Grassmann R, Fleckenstein B. 1989. Selectable recombinant herpesvirus saimiri is
capable of persisting in a human T-cell line. J Virol 63:1818-1821

Hunt R et al. 1970. Morphology of a disease with features of malignant lymphoma in
marmosets and owl monkeys inoculated with Herpesvirus saimiri. J Natl Cancer Inst
44:447-465.

Hunt R et al. 1972. Herpesvirus saimiri malignant lymphoma in spider monkeys. A new
susceptible host. J Med Primatol 1:114-120.

Hunt R et al. 1973. Spontaneous Herpesvirus saimiri lymphoma in an owl monkey. J
Infect is 127:723-725.

Hunt R et al. 1976. Herpesvirus saimiri lymphoma in owl monkeys (Aotus trivirgatus).
Susceptibility, latent period, hematologic picture and course. Theriogen 6:139-151.

Jayo MJ et al. 1988. Maxillo-orbital lymphoma (Burkitt's-type) in an infant Macaca
fascicularis. Lab Anim Sci 38:722-726.

Kamine J, Bakker A, Desrosiers RC. 1984. Mapping of RNA transcribed from a region
of the Herpesvirus saimiri genome required for oncogenicity. J Virol 52:532-540.

Kiyotaki M, Desrosiers RC, Letvin NL. 1986. Herpesvirus saimiri strain 11 immortalizes
a restricted marmoset T8 lymphocyte subpopulation in vitro. J Exp Med 164:926-931.

Medveczky MM et al. 1989. Herpesvirus saimiri strains from three DNA subgroups have
different oncogenic potentials in New Zealand white rabbits. J Virol 63:3601-3611.

Melendez LV et al. 1968. An apparently new herpesvirus from primary kidney cultures
of the squirrel monkey (Saimiri sciureus). Lab Anim Care 18:374-381.

Melendez LV et al. 1969. Herpesvirus saimiri. II. Further characterization studies of
a new virus from the squirrel monkey. Lab Anim Care 19:372-377.

Melendez LV et al. 1969. Herpesvirus saimiri. III. Experimentally induced malignant
lymphoma in primates. Lab Anim Care 19:378-386.

Melendez LV et al. 1974. Prevention of lymphoma in cotton-top marmosets by
Herpesvirus saimiri antiserum.  J Med Primatol 3:213-220.

Mohr FC, Bronson RT, Hunt RD. 1983. Failure of Herpesvirus saimiri to enhance
atherogenesis in owl monkeys (Aotus trivirgatus). Atherosclerosis 46:173-179.

Newbauer RH et al. 1974. Virological investigations of Herpesvirus saimiri infected owl
monkeys.  J Med Primatol 3:27-40.

Ortaldo JR et al. 1985. Cytotoxic activity of normal and Herpesvirus
saimiri-transformed nonhuman primate cells. Cell Immunol 95:349-357.

Pearson GR et al. 1974. Immunological and virological investigations on owl monkeys
infected with Herpesvirus saimiri.  J Med Primatol 3:54-67.

Rangan SRS et al. 1977. Herpesvirus saimiri-induced lymphoproliferative disease in
howler monkeys. J Natl Cancer Inst 59:165-171.

Wallen WC et al. 1974. In vitro immunological characteristics of lymphoid cells derived
from owl monkeys infected with Herpesvirus saimiri. J Med Primatol 3:41-53.

      (ii) Herpesvirus ateles type 2: From spider monkey.  Leukemia  and malignant
lymphoma in cottontop marmosets.

Hunt R et al. 1972. Pathologic features of Herpesvirus ateles lymphoma in cotton-
topped marmosets (Saguinus oedipus). J Natl Cancer Inst 49:1631-1639.

Melendez LV et al. 1972. A new lymphoma virus of monkeys: Herpesvirus ateles. Nature
235:182-184.

      (iii) Epstein-Barr virus and EBV-like viruses: Experimental disease with human
EBV in owl monkeys, gibbons, and cotton-top tamarins; naturally occurring viruses
in chimps and baboons.  Some experimental evidence indicates that survival may
depend on whether or not cell-mediated response occurs.

Bocker JF et al. 1980. Characterization of an EBV-like virus from African green
monkey lymphoblasts. Virology 101:291-295.

Deinhardt F et al. 1978. Susceptibility of marmosets to Epstein-Barr virus-like baboon
herpesvirus. Prim Med 10:163-170.

Epstein MA et al. 1973. Pilot experiments with EB virus in owl monkeys (Aotus
trivirgatus). I. Reticuloproliferative disease in an inoculated animal. Int J Cancer
12:309-318.

Epstein MA. 1976. EB virus in the owl monkey (Aotus trivirgatus). Lab Anim Sci
26:1127-1130.

Gerber P et al. 1977. Biologic and antigenic characteristics of Epstein-Barr virus
related herpesviruses of chimpanzees and baboons. Int J Cancer 20: 448-458.

Finerty S, Scullion FT, Morgan AJ. 1988. Demonstration in vitro of cell mediated
immunity to Epstein-Barr virus in cotton-top tamarins. Clin Exp Immunol 73:181-185.

Heller M, Gerber P, Kieff E. 1982. DNA of Herpesvirus pan, a third member of the
Epstein-Barr virus-Herpesvirus papio group. J Virol 41:931-939.

Lapin BA, Timanovskaya VV, Yakovleva LA. 1985. Herpesvirus HVMA: a new
representative in the group of the EBV-like B-lymphotropic herpesviruses of
primates. Hamatol Bluttransfus 29:312-313.

Levine PH. 1980. Infection of rhesus macaques and chimpanzees with Epstein-Barr
virus. Arch Virol 66:341-351.

Rangan SR et al. 1986. Epstein-Barr virus-related herpesvirus from a rhesus monkey
(Macaca mulatta) with malignant lymphoma. Int J Cancer 38:425-32.

Shope T et al. 1973. Malignant lymphoma in cotton-topped marmosets after inoculation
with Epstein-Barr virus. Proc Natl Acad Sci 70:2487-2491.

Werner J et al. 1972. Responses of gibbons to inoculation of Epstein-Barr virus. J
Infect Dis 126:679-681.

Werner J et al. 1975. Lymphoproliferative disease in cotton-topped marmosets after
inoculation with infectious mononucleosis-derived Epstein-Barr virus. Int J Cancer
15:1000-1008.

Voevodin AF et al. 1983. Increased antibody responses to Herpesvirus papio (HVP)
antigens in prelymphomatous baboons (Papio hamadryas) of the Sukhumi high
lymphoma stock.  Int J Cancer 32:637-639.

Young LS et al. 1989. Epstein-Barr virus gene expression in malignant lymphomas
induced by experimental virus infection of cottontop tamarins. J Virol 63:1967-1974.

2.    Cytomegaloviruses: Isolated from vervet, squirrel, owl monkeys and marmosets. 
Thought to occur in Cebus spp, chimp, tarsier.  Generalized disease is rare, but
reported in rhesus and gorilla.  Confirmation of the diagnosis may be complicated by
the possibility that nonhuman primate CMVs may not react with antisera against
human CMV.

Ablashi V et al. 1972. A cytomegalovirus isolated from an owl monkey.  Lab Anim Sci
33:190-195.

Nigida SM, Falk LA, Wolfe LG. 1979. Isolation of a cytomegalovirus from salivary
glands of white-lipped marmosets (Saguinus fuscicollis). Lab Anim Sci 29:53-60.

Swack NS, Hsiung G. 1982. Natural and experimental simian cytomegalovirus infections
at a primate center. J Med Primatol 11:169-177.

Vogel FS, Pinkerton H. 1955. Spontaneous salivary gland virus disease in
chimpanzees. Arch Pathol 60:281-288.

3.    SA-8:  An alpha herpesvirus, first isolated from vervet monkey; later from
baboons.  Papio spp. considered the natural hosts.  Persistent latent infection of
nerve ganglia, transmitted venereally--possible model of human genital herpes? 
Usually no disease, although an epizootic was reported in which males had lesions on
genitalia which began as patchy erythema and progressed to vesicles and coalescing
ulcers.  These were accompanied by regional lymphadenopathy.  Females had similar
lesions on the vulva, anus, and perineum.  A few animals also had herpetic lesions on
the lips and gums.  In some animals, the lesions only occurred once, then healed. 
Others had recurrences, and a few had persistent lesions.

Brack M et al. 1985. Experimental herpes neonatalis in SA8 infected baboons (Papio
cynocephalus). Lab Anim 19:125-131.

Eichberg J et al. 1973. Experimental herpesvirus infection of baboons (Papio
cynocephalus) and African green monkeys (Cercopithecus aethiops) and recovery of
virus by tissue explants.  Arch Ges Virusforsch 43:304-314.

Eichberg JW et al. 1976. Clinical virological, and pathological features of herpesvirus
SA8 infection in conventional and gnotobiotic infant baboons (Papio cynocephalus).
Arch Virol 50:225-270.

Eichberg JW et al. 1980. Immunoresponsiveness of herpesvirus SA8 infected infant
baboons. Dev Comp Immunol 4:137-146.

Kalter SS, Weiss SA, Heberling RL et al. 1978. The isolation of herpesvirus from
trigeminal ganglia of normal baboons (Papio cynocephalus).  Lab Anim Sci 28:705-709.

Levin JL et al. 1988. A naturally occurring epizootic of simian agent 8 in the baboon.
Lab Anim Sci 38:394-397.

Ochoa R et al. 1982. Herpesviral pneumonia and septicemia in two infant Gelada
baboons (Theropithecus gelada).  J Med Primatol 11:51-58.

4.    Rhesus leukocyte-associated herpesvirus.

Bissell JA et al. 1973. Rhesus leukocyte-associated herpesvirus: II. Natural and
experimental infection.  J Infect Dis 128:630-637.

Frank AL et al. 1973. Rhesus leukocyte-associated herpesvirus. I. Isolation and
characterization of a new herpesvirus recovered from rhesus monkey leukocytes.  J
Infect Dis 128:618-629.

5.    Spider monkey herpes virus (Herpesvirus ateles type 1):  Isolated in 1968 from
female spider monkey that died at California zoo with erosions and ulcers on lips,
nose, tongue, palate, and gums.  Thought to have been fatal infection in natural host
because antibodies have been detected in adult spider monkeys.

Hull RN et al. 1972. Recovery and characterization of a new simian herpesvirus from
a fatally infected spider monkey. J Natl Cancer Inst 49:225-230.

6.    H. aotus types 1, 2 and 3: Owl monkeys.

Ebeling A et al. 1983. Genome structure and virion polypeptides of the primate
herpesviruses Herpesvirus aotus types 1 and 3: comparison with human
cytomegalovirus. J Virol 45:715-726.

Fuchs PG et al. 1985. Genome organization of Herpesvirus aotus type 2. J Virol
53:13-18.

7.    Tree shrew herpesviruses: 5 types, none known to be pathogenic.

Darai G. 1982. Tree shrew herpesvirus. Dev Biol Stand 52:39-51.

8.    H. ateles type 3: Third herpesvirus isolated from spider
      monkeys.

9.    H. saguinus:  marmoset.


                   Miscellaneous References-Primate Herpesviruses

Ablashi V et al. 1979. Oncogenic herpesviruses of nonhuman primates. Comp Immunol
Microbiol Inf Dis 2:229-241.

Barahona H et al. 1974. A compendium of herpesvirus isolated from non-human
primates.  Intervirol 3:175-192.

Barahona H et al. 1980. The owl monkey (Aotus trivirgatus) as an animal model for
viral diseases and oncologic studies. Lab Anim Sci 26:1104-1112.

Falk LA. 1974. Oncogenic DNA viruses of nonhuman primates: A review. Lab Anim Sci
24:182-192.

Fleckenstein B. 1979. Oncogenic herpes viruses of nonhuman primates. Biochim
Biophys Acta 560:301-342.

Hilliard JK, Kalter SS. 1985. Development of molecular probes for simian herpesvirus
detection. Dev Biol Stand. 59:79-86.

Hunt R et al. Malignant lymphoma, Model No. 60. In Handbook Animal Models of Human
Disease, fasc. 5. Ed TC Jones, DB Hackel and G Migaki. Registry of Comparative
Pathology, AFIP, Washington, DC, 1976.

Hutt R. 1981. Detection of antibodies to Herpesvirus simiae and Herpesvirus hominis
in nonhuman primates. Lab Anim Sci 31:184-189.

Kalter SS, Hilliard JK, Heberling RL. 1982. The differential diagnosis of herpesvirus
infections in man and animals. Dev Biol Stand 52:101-113.

McCarthy K et al. 1975. A review of primate herpesviruses. Proc Royal Soc Med 68:145-
150.

Melendez LV et al. 1971. New herpesviruses from South American monkeys.
Preliminary report. Lab Anim Sci 21:1050-1054.

Melendez LV 1972. Two new herpesviruses from spider monkeys (Ateles geoffroyi). J
Natl Cancer Inst 49:233-237.

Melendez LV et al. Lymphoma virus of monkeys: Herpesvirus saimiri and Herpesvirus
ateles, the first oncogenic herpesviruses of primates. A review. In Oncogenesis and
Herpesviruses, International Agency for Research on Cancer, Lyon, pp 451-461, 1972.

Mou SW et al. 1986. Comparison of the primate alphaherpesviruses.  I. Characterization
of two herpesviruses from spider monkeys and squirrel monkeys and viral
polypeptides synthesized in infected cells. Arch Virol 91:117-133.

Rangan SRS. 1979. Tumors and viruses in nonhuman primates. Adv Virus Res 24:1-123.

Rasheed S. 1979. Herpesvirus of orangutan (H. pongo) and search for retrovirus in
nonhuman primates. Comp Immunol Microbiol Inf Dis 2:265-274.


                                  Measles (Rubeola)

1.    Agent:

      A paramyxovirus, genus Morbillivirus.
2.    Epizootiology:

      Macaques (especially rhesus), baboons, African green, marmosets, tamarins,
squirrel monkeys, chimps, and Presbytis cristatus are susceptible to human measles. 
Can be fatal if complicated by bacteria.  Not a disease of wild monkeys, but most wild-
caught monkeys seroconvert within a few months of capture.  Virus is shed in most
secretions and in urine.

3.    Clinical:

      Can be asymptomatic or rapidly fatal.  Marmosets are said to be especially
susceptible.  Course of clinical disease usually is less than 10 days, and is
characterized by maculopapular skin rash, serous to mucopurulent nasal discharge,
ocular discharge, maybe Koplik's spots, diarrhea, and rarely, abortion.  Immuno-
suppression during measles virus infection is clearly documented.

4.    Pathology:

      Interstitial pneumonia with syncytial giant cells in alveoli and bronchioles, with
nuclear and cytoplasmic inclusions.  This commonly is complicated by secondary
bacterial invaders, such as Streptococcus pneumoniae, resulting in suppurative
bronchopneumonia.  In such cases, the lesions due to the viral infection may be
obscured.  Skin lesions include focal acanthosis, hyperkeratosis, and parakeratosis;
hair follicle necrosis; epidermal and follicular giant cells; no inclusions.  Lymphoid
tissues can have syncytial giant cells (Warthin-Finkeldey cells).  Similar cells can
occur in the liver and transitional epithelium of the urinary tract, although these are
rare, and on occasion can be seen in other epithelia throughout the body and in the
choroid plexus.  It is more usual for transitional epithelium to have inclusions without
much cellular change.  Such inclusions must be differentiated from the nonspecific
inclusions in transitional epithelium of macaques, especially cynomolgus. 
Enterocolitis with inclusions in some cases.  Rarely, endometritis.

      SSPE-like disease reported in baboon.

5.    Diagnosis:

      Signs and lesions, virus isolation and identification, various serologic
techniques such as hemagglutination inhibition.  Remember that macaques, especially
cynomolgus, often have nonspecific inclusions in the urinary bladder epithelium that
resemble measles virus inclusions.

6.    Control:

      Keep known exposed personnel and children away from primates.  Newly
imported primates will have been exposed before reaching lab.  Zoonotic (monkeys can 
transmit  back to people).   Chick  embryo measles vaccine can be used.  Not
necessary if already exposed, but primates raised in closed colonies could be
susceptible; vaccine could be helpful prophylaxis.

7.    References:

Albrecht P et al. 1977. SSPE: Experimental infection in nonhuman primates. Science
195(4273):64-66.

Albrecht P et al. 1980. Fatal measles infection in marmosets. Pathogenesis and
prophylaxis. Infect Immun 27:969-978.

Frazer CEO et al. 1978. A paramyxovirus causing fatal gastroenterocolitis in marmoset
monkeys. Prim Med 10:261-270.

Fujimoto K et al. 1983. Immunoglobulins and measles antibody in sera of newborn
cynomolgus monkeys and in milk of their mothers. Jpn J Med Sci Biol 36:209-14.

Hall WC et al. 1971. Pathology of measles in rhesus monkeys.  Vet Path 8:307-319.

Kamahora J. 1965. Pathological and immunological studies of monkeys infected with
measles virus. Arch ges Virusforsch 16:161-167.

Kim LS et al. 1970. Subacute sererosing panencephalitis-like syndrome in the adult
baboon (Papio sp.). J Am Vet Med Assoc 157:730-735.

Klutch MJ et al. 1979. Fatal measles infection in marmosets. Proc Am Soc Microbiol. p.
308.

Levy BM, Mirkovic RR. 1971. An epizootic of measles in a marmoset colony. Lab Anim
Sci 21:33-39.

Lorenz D, Albrecht P. 1980. Susceptibility of tamarins to measles virus. Lab Anim Sci
30:661-665.

MacArthur JA et al. 1982. The effect of measles vaccination in rhesus monkeys (Macaca
mulatta).  Lab Anim 16:267-270.

Manning PJ et al. 1968. Naturally occurring giant cell pneumonia in the rhesus
monkey (Macaca mulatta). J Am Vet Med Assoc 153:899-904.

McChesney MB et al. 1989. Virus-induced immunosuppression: infection of peripheral
blood mononuclear cells and suppression of immunoglobulin synthesis during natural
measles virus infection of rhesus monkeys. J Infect Dis 159:757-760.

Montrey R et al. 1980. An epizootic of measles in captive silvered leaf monkeys
(Presbytis cristatus) in Malaysia. Lab Anim Sci 30:694-697.

Potkay S et al. 1966. An epizootic of measles in a colony of rhesus monkeys (Macaca
mulatta). Am J Vet Res 27:331-334.

Remfry J. 1976. A measles epizootic with five deaths in newly imported rhesus
monkeys (Macaca mulatta). Lab Anim 10:49-57.

Renne RA. 1973. Measles virus-associated endometritis, cervicitis, and abortion in a
rhesus monkey. J Am Vet Med Assoc 163:639-641.

Steele M et al. 1982. Spontaneous paramyxoviral encephalitis in nonhuman primates
(Macaca mulatta and M. nemestrina). Vet Pathol 19:132-139.

Welshman MD. 1989. Measles in the cynomolgus monkey (Macaca fascicularis). Vet Rec
124:184-186.


                                 Simian Adenoviruses

1. Agents:

      Many (> 20) serotypes isolated, some only from cell cultures.

2.    Epizootiology:

      Wide host range, some perhaps including man.  Common in gastrointestinal and
respiratory tracts, not usually pathogenic.

3.    Clinical:

      Mostly respiratory, if any.  Various serotypes associated with mild upper
respiratory signs and conjunctivitis or "pneumoenteritis."  Diarrhea reported in
experimental disease.  Usually subclinical in adults.  Fatalities reported mostly in
neonatal macaques (rhesus, bonnet, pigtailed, cynomolgus); African green and
baboons also susceptible.

4.    Pathology:

      Necrotizing bronchiolitis, multifocal necrotizing pneumonitis, and interstitial
pneumonia.  Typical nuclear inclusions in epithelial cells.

      Necrotizing pancreatitis due to adenoviral infection has been reported.

      Several serotypes are oncogenic in newborn hamsters (lymphomas, sarcomas).

5.    Diagnosis:

      Morphology, virus isolation and identification.
6.    Control:

      No vaccine available.

7.  References:

Boyce JT, Giddens WE Jr, Valerio M. 1978. Simian adenoviral pneumonia. Am J Pathol
91:259-276.

Chandler FW, McClure HM. 1982. Adenoviral pancreatitis in rhesus monkeys: Current
knowledge. Vet Pathol 19(Suppl 7):171-180.

Darai G et al. 1980. An adenovirus from Tupaia (tree shrew). Growth of the virus,
characterization of viral DNA, and transforming ability. Virol 104:122-138.

Eugster AK et al. 1969. Isolation of adenoviruses from baboons (Papio sp.) with
respiratory and enteric infections. Arch ges Virusforsch 26:260.

Landon JC, Bennett G. 1969. Viral induced simian conjunctivitis. Nature 222:683-684.

Li QG, Wadell G. 1989. The degree of genetic variability among adenovirus type 4
strains isolated from man and chimpanzee. Arch Virol 101:65-77.

Merkow LP, Slifikin M. 1973. Simian adenoviruses. Progr Exp Tumor Res 18: 67.

Moe JB et al. 1979. Experimental adenovirus (SV-20) pneumonia in fetal rhesus
monkeys. Lab Invest 41:211-219.

Moe JB et al. Fetal pneumonia, Model No. 210. In Handbook: Animal Models of Human
Disease, Fasc 9, ed. CC Capen, DB Hackel, TC Jones, and G Migaki. Registry of
Comparative Pathology, AFIP, Washington, DC, 1980.

Moe JB, Osburn BI. 1983. Fetal and maternal immunologic manifestations of
intrauterine Adenovirus SV-20 infection. Vet Immunol Immunopathol 4:319-32.

Ohtaki S, Kato K. 1989. Simian adenovirus type 7 (SA-7) induces tumours of
nerve-supporting or paraneural cell origin in newborn hamsters. Br J Exp Pathol
70:415-424.

Schoeb TR, DaRif CA. 1984. Adenoviral infection in infant tree shrews. J Am Vet Med
Assoc 185:1363-1366.

Shortridge KF et al. 1976. Serological evidence of human adenovirus infections in
animals. J Comp Pathol 86:629-635.

Shroyer EL et al. 1979. Three serologic types of adenovirus infection of owl monkeys.
Am J Vet Res 110:532-536.
Wigand R, Mauss M, Adrian T. 1989. Chimpanzee adenoviruses are related to four
subgenera of human adenoviruses. Intervirology 30:1-9.



                          Miscellaneous Respiratory Viruses

1.    Agents:

      (i) Influenza (orthomyxovirus). Gibbons.

      (ii) Parainfluenza type 1 (paramyxovirus). Marmosets.

      (iii) Parainfluenza type 3 (paramyxovirus). Patas monkeys and
      gibbons.

      (iv) Respiratory syncytial virus (pneumovirus). Chimp.

      (v) Reoviruses (Reoviridae). Apes.

      (vi) Rhinoviruses (Picornaviridae). Apes.

      (vii) SV5, SV41 (paramyxoviruses).

2.    Disease:

      None (SV5, SV41) to mild upper respiratory disease (most) to moderately severe
respiratory disease with bronchitis (influenza).  Infection seldom significant in itself
but may predispose to bacterial pneumonia, a major cause of morbidity and mortality
among captive nonhuman primates.

3.    References:

Belshe RB et al. 1977. Experimental respiratory syncytial virus infection of four
species of primates. J Med Virol 1:157-162.

Churchill AE. 1963. The isolation of parainfluenza-3 virus from fatal cases of
pneumonia in Erythrocebus patas monkeys.  Br J Exp Pathol 44:529-557.

Flecknell PA et al. 1983. Respiratory disease associated with parainfluenza type 1
(Sendai) virus in a colony of marmosets (Callithrix jacchus). Lab Anim 17:111-113.

Fraser CEO et al. 1978. A paramyxovirus causing fatal gastroenterocolitis in marmoset
monkeys. Prim Med 10:261-270.

Johnson DO et al. 1971. An epizootic of A2/Hong Kong/68 influenza in gibbons. J Infect
Dis 123:365-370.
Jones EE et al. 1984. Predisposition to invasive pneumococcal illness following
parainfluenza type 3 virus infection in chimpanzees. J Am Vet Med Assoc 185:1351-
1353.

Martin P, Kaye HS. 1983. Epizootic of parainfluenza-3 virus infection in gibbons. J Am
Vet Med Assoc 183:1185-1187.

Murphy BR et al. 1983. Evaluation of the A/Seal/Mass/1/80 virus in squirrel monkeys.
Infect Immun 42:424-6.

Richardson LS et al. 1978. Experimental respiratory syncytial virus pneumonia in
cebus monkeys. J Med Virol 2:45-59.

Richardson-Wyatt LS 1981. Respiratory syncytial virus antibodies in nonhuman
primates and domestic animals. Lab Anim Sci 31:413-415.

Sutherland SD et al. 1986. Rapid diagnosis and management of parainfluenza 1 virus
infection in common marmosets (Callithrix jaccus). Lab Anim 20:121-126.


                                      Monkeypox

1.    Agent:

      A poxvirus antigenically related to smallpox and vaccinia viruses.

2.    Epizootiology:

      Reported in rhesus and cynomolgus macaques, owl-faced monkeys
(Cercopithecus hamlyn), gorillas, gibbons, squirrel monkeys, marmosets, chimpanzees,
and humans.  Occurs naturally in West and Central Africa.  A high prevalence (24.7%)
of monkeypox-specific antibodies was found in two species of squirrels (Funisciurus
anerythrus and  Heliosciurus rufobrachium), suggesting that these animals may serve
as reservoirs or vectors.  (The animals commonly are trapped by natives.)  Three of
39 primates were seropositive for monkeypox, but as yet it is not known whether
primates maintain the virus or, like humans, are merely occasional hosts.  About 10
or so outbreaks in captive primates have been reported.  Apes appear to be quite
susceptible.

3.    Clinical:

      Fever, "pocks" over trunk, tail, face, and limbs, including palms and soles.  Wide
range of susceptibility: in some, general health unaffected but others become ill and
some die.

4.    Pathology:

      Pathogenesis is classical for systemic poxviral disease, with local multiplication,
primary viremia, secondary internal multiplication, secondary viremia, disseminated
pox.
      Skin lesions begin as firm elevations resulting from epithelial proliferation.  As
"ballooning" degeneration then necrosis proceed from the center outward, lesions
develop into umbilicated pustules ("pocks").  Crusts then form over healing lesions. 
Other lesions include multifocal necrotizing pneumonitis, orchitis, and lymphadenitis
with lymphoid hyperplasia.

5.    Diagnosis:

      Microscopic exam of lesion scrapings, morphology, EM, virus isolation.

6.    Control:

      An uncommon disease.  Common sense and good colony management should
suffice.

7.    References:

Arita I et al. 1972. Outbreaks of monkey pox and serological surveys in nonhuman
primates.  Bull WHO 46:625-631.

Arita I et al. 1985. Human monkeypox: A newly emerged orthopoxvirus zoonosis in the
tropical rain forests of Africa. Am J Trop Med Hyg 34:781-789.

Bourke ATC, Dumbell KR. 1972. An unusual pox virus from Nigeria. Bull WHO 46:621-
623.

Cho CT, Wenner WA. 1973. Monkey pox virus. Bacteriol Rev 37:1-18.

Foster SO et al. 1972. Human monkey pox. Bull WHO 46:569-576.

Heberling RL, Lalter SS. 1971. Induction, course, and transmissibility of monkey pox
in the baboon (Papio cynocephalus). J Infect is 124:33-38.

Janseghers L et al. 1984. Fatal monkeypox in a child in Kikwit, Zaire. Ann Soc Belg
Med Trop 64:295-298.

Khodakevich L et al. 1987. Monkeypox virus in relation to the ecological features
surrounding human settlements in Bumba zone, Zaire. Trop Geogr Med 39:56-63.

Khodakevich L et al. 1987. The role of squirrels in sustaining monkeypox virus
transmission. Trop Geogr Med 39:115-122.

Lourie G et al. 1972. Human infection with monkey pox virus. Laboratory investigation
of six cases in West Africa. Bull WHO 46:633-639.
Marennikova SS et al. 1972. Isolation and properties of the causal agent of a new
variola-like disease (monkey pox) in man.  Bull WHO 46:599-611.

Mutombo M. 1983. Human monkey pox transmitted by a chimpanzee in a tropical rain
forest area of Zaire. Lancet 1(8237):735-737.

Stagles MJ et al. 1985. The histopathology and electron microscopy of a human
monkeypox lesion. Trans R Soc Trop Med Hyg 79:192-202.

_____. 1984. Human monkeypox: The past five years. WHO Chron 38:227-229.


                     Benign Epidermal Monkeypox (BEMP, Tana Pox)

1.    Agent:

      A pox virus antigenically related to Yaba virus but not to vaccinia and smallpox. 
Syn. OrTeCa virus.

2.    Epizootiology:

      Disease of man and monkeys in Kenya in late 1950s and early 1960s.  Appeared
simultaneously in macaques and handlers in labs in Oregon, Texas, and California
(hence "OrTeCa") in mid 1960s, and slightly later in Maryland.  In the first 3 labs the
animals were from a single importer, where the disease was also seen.  May not be
indigenous monkey disease; if not, natural host unknown.

3.    Clinical:

      In rhesus monkeys, typical pocks on face, arms and perineum, without general
illness.  Most affected people have only localized lesions, e.g., at sites of scratches
on hands and arms, but some had regional lymphadenopathy, fever, and debility, and
a few had generalized pocks.

4.    Pathology:

      Similar to monkey pox.  Sequential epidermal changes of proliferation
(acanthosis), necrosis, sloughing, and healing.  However, proliferation tends to
extend into hair follicles.  Cytoplasmic inclusions are numerous, nuclear vacuoles
occur which reportedly help differentiate from monkey pox.  No visceral lesions
reported.

5.    Diagnosis:

      As for monkeypox.

6.    Control:
      ?--Apparently has not occurred since original outbreak.

7.    References:

Casey HW et al. 1967. Electron microscopy of a benign epidermal pox disease of rhesus
monkeys. Am J Pathol 51:443-446.

Downie AW, Espana C 1972. Comparison of tanapox and Yaba-like viruses causing
epidemic disease in monkeys. J Hyg 70:23-32.

Hall AS, McNulty WP. 1967. A contagious pox disease in monkeys. J Am Vet Med Assoc
151:833-838.

Kupper JC. 1970. Experimental Yaba and benign epidermal monkey pox in rhesus
monkeys.  Lab Anim Sci 20:979-988.

McNulty WP et al. 1968. A pox disease in monkeys transmitted to man. Clinical and
histological features. Arch Dermatol 97:386-293.


                                     Yaba Virus


1.    Agent:

      A poxvirus serologically unrelated to the vaccinia group but related to OrTeCa
virus.

2.    Epizootiology:

      Not understood; may be a natural indigenous infection of wild African primates. 
Subcutaneous tumors in rhesus monkeys and a baboon in Yaba, Nigeria in the late
1950s were shown to be caused by a pox virus.  Mode of transmission obscure, but
experimentally can be done by aerosol, direct inoculation.  Man, cynomolgus, rhesus,
stumptailed, and pigtailed macaques, African green monkeys, sooty mangabeys and
patas monkeys are susceptible.
Apparently common.

3.    Clinical:

      Rapidly growing subcutaneous masses which spontaneously regress in a few
weeks.

4.    Pathology:

      Proliferation of large "histiocytes" in dermis or other connective tissue (internal
tumors occurred after IV inoculation).  Cytoplasmic inclusions are usually visible. 
Multinucleate giant cells appear with regression, which is accompanied by
lymphocytic and plasmacytic reaction.

5.    Diagnosis:

      Signs and lesions, EM, virus isolation.

6.    References:

Behbehani AM et al. 1968. Yaba tumor virus. I. Studies on pathogenesis and immunity.
Proc Soc Exp Biol Med 129:556-561.

Bruestle ME et al. 1981. Naturally occurring Yaba tumor in a baboon (Papio papio). Lab
Anim Sci 31:392-394.

Grace JT, Mirand EA. 1963. Human susceptibility to a simian tumor virus. Ann NY Acad
Sci 108:1123-1128.

Kupper JL. 1970. Experimental Yaba and benign epidermal monkey pox in rhesus
monkeys. Lab Anim Sci 20:979-988.

Spencer AJ. Diagnostic exercise. 1985. Subcutaneous nodules in rhesus monkeys. Lab
Anim Sci 35:79-80.

Tsuchiya y, Tagaya I. 1971. Sero-epidemiological survey on Yaba and 1211 virus
infections among several species of monkeys. J Hyg 69:445-451.

Whittaker D, Glaister JR. 1985. A Yaba-like condition in a young baboon. Lab Animal
19:177-179.

Wolfe LG et al. 1968. Experimental aerosol transmission of Yaba virus in monkeys. J
Natl Cancer Inst 41:1175-1195.


                                Molluscum Contagiosum

1.    Agent:

      Poxvirus of man, unrelated to smallpox or vaccinia, never isolated but has
poxvirus ultrastructure.

2.    Epizootiology:

      Mildly contagious disease, mostly of children.  One report of disease in chimps.

3.    Clinical:

      Proliferative lesions mostly around the eyes in chimps.

4.    Pathology:

      Very characteristic.  Verrucous or plaque-like lesions characterized by extreme
epidermal proliferation.  Very large inclusions.

5.    Diagnosis:

      Morphology, EM.

6.    Reference:

Douglas J et al. 1967. Molluscum contagiosum in chimpanzees. J Am Vet Med Assoc
151:901-904.


                              Simian Hemorrhagic Fever

1.    Agent:

      Complete classification not yet assigned.  Tentatively, genus Pestivirus
(Togaviridae).

2.    Epizootiology:

      Asymptomatic infections in patas monkeys, vervet monkeys, and baboons.  Patas
monkeys thought to be natural host; about 50% of wild patas monkeys have
antibodies, much less prevalent in vervets and baboons.  Some patas monkeys, maybe
about 10%, are asymptomatic carriers.  In macaques (M. mulatta, M. fascicularis, M.
arctoides, M. assamensis, M. nemestrina) epizootics of acute severe disease with high
mortality.  (Mortality can ÷100%.) Seen in Washington DC, California, Russia, and
England.  Puzzling: epizootics have occurred in when macaques introduced into
macaque colonies, without obvious exposure to patas monkeys--source unclear.

3.    Clinical:

      Rapid onset, fever, facial edema, cyanosis, anorexia, melena; cutaneous,
subcutaneous, and retrobulbar hemorrhage; thrombocytopenia.  Course 10-15 days.

4.    Pathology:

      Hemorrhages in any tissue, especially skin, nasal mucosa, lung, gastrointestinal
tract, renal capsule and perirenal tissue.  Hemorrhagic necrosis of the duodenal
mucosa, distinctly demarcated at the pylorus, usually present.  There is also
splenomegaly with hemorrhagic necrosis of the lymphoid areas; necrosis of the lymph
nodes, Peyer's patches, and tonsils; and many thrombi in small veins and capillaries. 
Disseminated intravascular coagulation is an important component of the pathogenesis
of the disease.

5.    Diagnosis:

      Signs and lesions, virus isolation, serologic test in survivors.

6.    Control:

      Keep primate species separate; proper hygeine.  Serologic tests cannot
distinguish carriers from previously infected, and virus isolation is unreliable for
diagnosis.

7.    References:

Abilgaard C et al. 1975. Simian hemorrhagic fever: Studies of coagulation and
pathology. Am J Trop Med Hyg 24:537-544.

Allen AM et al. 1972. Simian hemorrhagic fever. II. Studies in pathology. Am J Trop
Med Hyg 17:413-421.

Giddens WE et al. 1975. The pathogenesis of simian hemorrhagic fever: Hematologic
and histopathologic studies. Lab Invest 32:424-___.

Gravell M et al. 1980. Simian hemorrhagic fever (SHF): New virus isolate from a
chronically infected patas monkey.  J Gen Virol 51:99-106.

Gravell M et al. 1980. Methods to detect asymptomatic carriers of simian hemorrhagic
fever virus.  Lab Anim Sci 30:988-991.

Gravell M et al. 1980. Studies on simian hemorrhagic fever virus infection of patas
monkeys. I. Serology. In The Comparative Pathology of Zoo Animals, ed. Montali RJ,
Migaki G, Smithsonian Institution Press, Washington, DC, pp. 167-170.

Gravell M et al. 1982. Method to eliminate persistent simian hemorrhagic fever virus
infection of patas monkeys (Abstract). Lab Anim Sci 32-427.

London WT. 1977. Epizootiology, transmission and approach to prevention of fatal
simian hemorrhagic fever in rhesus monkeys. Nature 268:344-345.

London WT et al. 1982. Problems associated with treatment and prophylaxis of simian
hemorrhagic fever (SHF) in macaques (Abstract). Lab Anim Sci 32:427-   .

Madden L et al. 1968. Antigenic relationship of two strains of simian hemorrhagic
fever virus.  Lab Anim Sci 28:422-427.

Palmer AE et al. 1968. Simian hemorrhagic fever. Am J Trop Med Hyg 17:404-431.
Tauraso WM et al. 1968. Simian hemorrhagic fever. III. Isolation and characterization
of a viral agent. Am J Trop Med Hyg 17:423-431.

Trousdale M et al. 1975. Simian hemorrhagic fever virus: A new togavirus (3911). Proc
Soc Exp Biol Med 150:707-711.


                                    Yellow Fever

1.    Agent:

      Genus Flavivirus, Togaviridae.

2.    Epizootiology:

      A disease of Central and South America and Africa.  In urban areas passed from
person to person by mosquito (Aedes spp.).  In the wild many mammals are natural
hosts, including the primate genera Alouatta, Ateles, Callicebus, Cebus, Marikina, and
Saimiri.  Man is only an accidental host.  Transmitted among day-sleeping monkeys
by day-feeding tree-living mosquitos.  Alouatta spp. are especially susceptible. 
Disease less severe in African
primates.  Rhesus monkeys susceptible but no natural disease in Asia.

3.    Clinical:

      In man, fever, muscular aches, headaches, jaundice, nausea and vomiting
(sometimes with blood)-- "black vomit"), hemorrhage, leukopenia, albuminuria.

4.    Pathology:

      Icterus, hemorrhage, severe midzonal hepatocellular necrosis with "Councilman
bodies."

5.    Diagnosis:

      Lesions, demonstration of virus.

6.    Control:

      Mosquito control.  Monkeys from areas where enzootic must be shipped in
mosquito-proof cages and examined for evidence of yellow fever if dead within 10
days.

7.    References:

Bearcroft WCG 1957. The histopathology of the liver of yellow fever-infected rhesus
monkeys. J Pathol Bacteriol 74:295-303.
Bearcroft WCG 1962. Electron microscope studies on the livers of yellow fever infected
African monkeys. J Pathol Bacteriol 83:59-64.

Pinheird FB. 1981. An epidemic of yellow fever in central Brazil 1972-1973 II.
Ecological studies. Am J Trop Med Hyg 30:204-211.

Smetana HF. 1962. The histopathology of experimental yellow fever. Virch Arch Pathol
Anat 335:411-427.


                                    Marburg Virus

1.    Historical:

      Marburg disease was first recognized in 1967.  Severe disease in lab workers in
Germany and Yugoslavia working with tissue cultures from African green monkeys
from Uganda; 7/30 affected died.  Monkeys not ill in German lab but there were
deaths among new monkeys in Yugoslav lab.  Since then, sporadic in Africa.

2.    Agents:

      Previously thought to be rhabdoviruses, these agents are morphologically quite
different from Vesiculovirus spp. (vesicular stomatitis group) and Lyssavirus spp.
(rabies group).  Some authors propose that Marburg virus and the similar Ebola virus
be placed in a new, as yet not official, family, the Filoviridae.

3.    Epizootiology:

      Transmission by aerosol, handling infected tissue, saliva, urine.  Monkeys are
susceptible to even small doses of virus; thus are probably not natural or reservoir
host.  If this be true, the natural host is unknown.  Antibodies to these viruses are
found at low prevalence rates in wild-caught primates in Kenya, but the significance
of this is not known.

4.    Clinical:

      (i). Man: 5-8 day incubation.  Fever, headache, impaired consciousness, vomiting,
diarrhea, rash, conjunctivitis, lymphadenopathy, hemorrhagic diathesis.

      (ii). Experimental disease in African green, rhesus, and squirrel monkeys:
Febrile until about 24 hours before death, then temperature dropped to subnormal;
diarrhea, rash, dyspnea, course 6-13 days, uniformly fatal.

5.    Pathology:

      (i). Man: Cerebral edema, multifocal necrosis of many tissues especially liver,
lymphoid tissue, kidney, pancreas, adrenal, and skin; lymphocytic encephalitis.
      (ii). Monkeys: Similar to man.  Multifocal to diffuse hemorrhagic necrosis of liver,
spleen, lungs; lymphoid necrosis, multifocal interstitial pneumonia, pulmonary
vasculitis.

6.    Diagnosis:

      Signs and lesions, virus isolation and identification.  Marburg and Ebola
diseases are indistinguishable.

7.    Control:

      Effective measures unknown--source unknown.  Use care when working with
African green monkeys and cells derived from them.

8.    References:

Anon. 1980. Marburg virus in Kenya. Lab Prim Newsletter 19:10-11.

Bowen ETW et al. 1978. Ebola hemorrhagic fever: Experimental infection of monkeys.
Trans Royal Soc Trop Med Hyg 72:188-191.

Conrad JL et al. 1978. Epidemiologic investigation of Marburg virus disease, Southern
Africa, 1975. Am J Trop Med Hyg 27:1210-1215.

Ellis S et al. 1979. Ebola virus: A comparison at ultrastructural level of the behavior
of the Sudan and Zaire strains in monkeys. Br J Exp Pathol 59:584-593.

Gear JSS et al. 1975. Outbreak of Marburg virus disease in Johannesburg. Brit Med
J 4:489-493.

Gordon-Smith CE et al. 1967. Fatal human disease from vervet monkeys. Lancet 2:1119-
1121.

Johnson BK et al. 1982. Marburg, Ebola and Rift Valley Fever virus antibodies in East
African primates. Trans R Soc Trop Med Hyg 76:307-310.

Johnson BK. 1981. Marburg and Ebola virus antibodies in Kenyan primates. Lancet 1
(8235):1420-1421.

Johnson KM et al. 1977. Isolation and partial characterization of a new virus causing
acute hemorrhagic fever in Zaire. Lancet 1:569-572.

Kiley MP et al. 1988. Physicochemical properties of Marburg virus: evidence for three
distinct virus strains and their relationship to Ebola virus. J Gen Virol 69:1957-1967.

Kissling RE et al. 1970. Marburg virus. Ann NY Acad Sci 174:932-945.

Morbidity and Mortality Weekly Report 29:145-146.

Simpson IH. 1969. Marburg agent disease: In monkeys. Trans Royal Soc Trop Med Hyg
63:303-309.

Smith H et al. 1982. Marburg-virus disease in Kenya. Lancet 1(8276):816-820.

Zlotnik I. 1969. Marburg agent disease: Pathology. Trans Royal Soc Trop Med Hyg
63:310-323.


                          Miscellaneous Hemorrhagic Fevers

1.    Dengue Fever

      (i). Agent: Genus Flavivirus (Togaviridae).

      (ii). Epizootiology: Southeast Asia, Mediterranean area, South Africa, Central
      America, and Hawaii. Monkeys are reservoir.  Spread to man by Aedes aegypti.

      (iii). Disease: In man, mild (fever, lymphadenopathy, rash) to severe
      (hemorrhagic fever).  In monkeys, no disease to forms similar to those in man
      but usually without rash.

      (iv). Control: Mosquito control; vaccination.

      (v). References:

Halstead SB et al. 1973. Studies on the pathogenesis of Dengue infection in monkeys.
I. Clinical laboratory responses to primary infection. II. Clinical laboratory responses
to heterologous infection. III. Sequential distribution of virus in primary and
heterologous infections. J Infect Dis 128:7-30.

Marchette NN, Halstead SB. 1974. Immunopathogenesis of Dengue infection in the
rhesus monkey. Transplantation Proc. 6:197-201.

Sabin AB. 1959. Dengue. In Viral and Rickettsial Infections of Man, ed. TM Rivers. JB
Lippincott, Philadelphia, pp 361-372.

Yuwono J et al. 1984. Seroepidemiological survey on dengue and Japanese encephalitis
virus infections in Asian monkeys. Southeast Asian J Trop Med Public Health 15:194-
200.

2.    Kyasanur Forest Disease

      (i). Agent: a Flavivirus.

      (ii). Epizootiology: Langurs (Presbytis entellus), bonnet macaques, and man in
      India.

      (iii).  Disease: Similar to Dengue fever.

      (iv). References:

Shah KV. 1965. Experimental infection of lactating monkeys with Kyasanur Forest
disease virus. Acta Virol (Prague) 9:72-75.

Singh KR et al. 1963. Experimental transovarial transmission of Kyasanur Forest
disease virus in Haemaphysalis spinigera. Nature 199:513.

Webb HE, Burton J. 1966. Clinical and pathological observations with special reference
to the nervous system in Macaca radiata infected with Kyasanur Forest disease virus.
Trans Royal Soc Trop Med Hyg 60:325-331.

Work TH. Kyasanur Forest disease. Progr Med Virol 1:248, 1958.

Work TH et al. 1959. Virological epidemiology of the 1958 epidemic of Kyasanur Forest
disease. Am J Publ Hlth 49:869-874.

3.    Other

Gonzalez PH et al. 1983. Junin virus infection of Callithrix jacchus: pathologic
features. Am J Trop Med Hyg 32:417-423.

Johnson BK et al. 1982. Marburg, Ebola and Rift Valley Fever virus antibodies in East
African primates. Trans R Soc Trop Med Hyg 76:307-310.

Gear JH. 1989. Clinical aspects of African viral hemorrhagic fevers. Rev Infect Dis
11(Suppl 4):S777-S782.


                                   Viral Hepatitis

1.    Agents:

      Hepatitis A virus is a picornavirus; hepatitis B virus, a hepadnavirus; the delta
or hepatitis D agent is an unclassified, defective RNA virus; and non-A-non-B agents
are not identified with certainty.

2.    Epizootiology:

      (i) Hepatitis A ("infectious hepatitis") in man is transmitted by fecal-oral route. 
Monkeys and apes get from man.  Serologic evidence of infection in chimps,
marmosets, baboons, and patas, African green, and Cebus monkeys.  Chimps and
marmosets susceptible to overt disease (marmosets used as model), in others
inapparent.  Zoonotic.  Human hepatitis A has a short icubation period and is
generally mild with very low mortality.

      (ii) Hepatitis B ("serum hepatitis") in man is usually transmitted in blood or
serum but can be transmitted by contact or indirectly since virus is in most
secretions.  Chimps and other apes and monkeys (including rhesus) are readily
infected (experimental in chimps and gibbons; evidence for natural infection in chimp,
baboon, squirrel monkey).  Zoonotic.  Human hepatitis B has a long incubation period,
and there can be carriers with or without hepatitis.  The disease may be manifested
as acute hepatitis which infrequently is fulminant.  Chronic hepatitis occurs in many
cases; it can be self-limiting or progressive, and can be fatal.  The HBs Ag is the viral
coat antigen; many of the particles are not infective, having no core, but there are
lots of them in the blood.  Chronic hepatitis B can be associated with hepatic
carcinoma.

      (iii) The delta or hepatitis D agent, which is a defective virus that replicates
only in the presence of HBV, typically causes a more virulent disease than
uncomplicated hepatitis B, more frequently resulting in progressive cirrhosis and
eventual liver failure.

      (iv) Non-A-non-B hepatitis in man is transmitted primarily via blood or serum
and is the major cause of post-transfusion hepatitis.  NANB hepatitis tends to be
chronic.  There are probably two (possibly more) forms of NANBH: hepatitis C, which
is transmitted parenterally, and an epidemic form, which is transmitted enterically. 
Agent(s) can persist for up to 6 years.  NANBH has been experimentally transmitted
to chimps.  Zoonotic?

3.    Clinical:

      Usually inapparent but can have fever, jaundice, even death.

4.    Pathology:

      Resembles that in man: Hepatocellular degeneration and necrosis which is
multifocal or irregular but tends to greater severity in the centrilobular zone,
accompanied by Kupffer cell hyperplasia and mononuclear inflammatory response. 
Inflammatory infiltrates tend to be mostly portal, but there can be some around the
central veins also, and in sinusoids depending on severity.  Chronic active NANB
hepatitis reported in chimps.

5.    Diagnosis:

      Serologic, morphologic.

6.    Control:

      Hygiene, training of personnel, exclusion of any known infected persons,
prophylactic immune globulin for handlers.

7.    References:

Abe K, Shikata T. 1982. Fulminant type A viral hepatitis in a chimpanzee. Acta Pathol
Jpn 32:143-148.

April M. Non-A, Non-B Hepatitis, Model No. 221. In Handbook: Animal Models of Human
Disease, fasc. 10. Ed. by CC Capen, DB Hackel, TC Jones, and G Migaki. Registry of
Comparative Pathology, AFIP, Washington, DC, 1981.

Barker LF et al. 1973. Transmission of type B viral hepatitis to chimpanzees. J Infect
Dis 127:648-662.

Berthelot P et al. 1984. Hepatitis B vaccine safety monitoring in the chimpanzee:
Interpretation of results. J Med Primatol 13:119-134.

Bradley DW et al. 1987. Enterically transmitted non-A, non-B hepatitis: Serial passage
of disease in cynomolgus macaques and tamarins and recovery of disease-associated
27- to 34-nm viruslike particles. Proc Natl Acad Sci USA 84:6277-6281.

Burke DS et al. 1981. Hepatitis A virus in primates outside captivity. Lancet 2:928.

Cote PJ et al. 1986. Protection of chimpanzees from type B hepatitis by immunization
with woodchuck hepatitis virus surface antigen. J Virol 60:895-901.

Coulepis AG. 1982. Biophysical and biochemical characterization of hepatitis A virus.
Intervirol 18:107-127.

Deinhardt F. et al. 1967. Studies on the transmission of human viral hepatitis to
marmoset monkeys. I. Transmission of disease, serial passages, and description of
liver lesions. J Exp Med 125:673-688.

Dienstag JL. 1976. Pathology of hepatitis A and B in chimpanzees.  Am J Pathol 85:131.

Eichberg JW, Kalter SS. 1980. Hepatitis A and B: Serologic survey of human and
nonhuman primate sera. Lab Anim Sci 30:541-543.

Holmes AW et al. 1973. Specific neutralization of human hepatitis type A in marmoset
monkeys. Nature (Lond) 243:419-420.

Jensen DM et al. 1984. Antibodies directed against human liver specific membrane
lipoprotein (LSP) in marmosets experimentally infected with the hepatitis A virus. Clin
Exp Immunol 55:535-540.

Karayiannis P et al. 1989. Studies of GB hepatitis agent in tamarins. Hepatology
9:186-192.

Keenan CM et al. 1984. Pathology of hepatitis A infection in the owl monkey (Aotus
trivirgatus). Am J Pathol 115:1-8.

Keenan CM et al. 1987. Animal models of human disease: Hepatitis A infection in the owl
monkey. Comp Pathol Bull 19:3-5.

Kessler H. et al. 1982. Hepatitis A and B at the London Zoo. J Infect 4:63-67.

Korba BE et al. 1986. Hepadnavirus infection of peripheral blood lymphocytes in vivo:
Woodchuck and chimpanzee models of viral hepatitis. J Virol 58:1-8.

Kornegay RW et al. 1985. Subacute nonsuppurative hepatitis associated with hepatitis
B virus infection in two cynomolgus monkeys. Lab Anim Sci 35:400-404.

Kos A et al. 1987. Biological and molecular characterization of the hepatitis delta
virus. Prog Clin Biol Res 234:83-87.

Krawczynski K et al. 1979. Immunopathologic aspects of the HBsAG carrier state in
chimpanzees. J Med Primatol 8:222-232.

Krawczynski KK et al. 1981. Pathogenetic aspects of hepatitis A virus infection in
enterally inoculated marmosets. Am J Clin Pathol 76:698-706.

Lankas GR, Jensen RD. 1987. Evidence of hepatitis A infection in immature rhesus
monkeys. Vet Pathol 24:340-344.

Lapin BA, Shevtsova ZV. 1989. Sensitivity of the Old World monkeys to hepatitis A
virus (spontaneous and experimental infection) [letter] Exp Pathol 36:63-64.

LeDuc JW, Escajadillo A, Lemon SM. 1981. Hepatitis A virus among captive Panamanian
owl monkeys (letter). Lancet 2(8260-61):1427-1428.

LeDuc JW et al. 1983. Experimental infection of the New World owl monkey (Aotus
trivirgatus) with hepatitis A virus. Infect Immun 40:766-772.

Lemon SM, Binn LN. 1983. Serum neutralizing antibody response to hepatitis A virus.
J Infect Dis 148:1033-1039.

Lemon SM et al. 1982. Transmission of hepatitis A virus among recently captured
Panamanian owl monkeys. J Med Virol 10:25-36.

Lemon SM. 1985. Type A hepatitis: New developments in an old disease. N Engl J Med
313:1059-1067.

Lemon SM. 1987. Genomic heterogeneity among human and nonhuman strains of
hepatitis A virus. J Virol 61:735-742.

Lucke VM, Bennett AM. 1982. An outbreak of hepatitis in marmosets in a zoological
collection. Lab Anim 16:73-77.

Maeda T et al. 1989. Production of antibodies directed against microtubular
aggregates in hepatocytes of chimpanzees with non-A, non-B hepatitis. J Gen Virol
70:1401-1407.

Mao JS et al. 1981. Susceptibility of monkeys to human hepatitis A virus. J Infect Dis
144:55-60.

Mascoli CC et al. 1973. Recovery of hepatitis agents in the marmoset from human cases
occurring in Costa Rica. Proc Soc Exp Biol Med 142:276-282.

Maynard JE. 1972. Experimental infection of chimpanzees with the virus of hepatitis
B. Nature (Lond) 237:514-515.

Negro F et al. 1988. Chronic hepatitis D virus (HDV) infection in hepatitis B virus
carrier chimpanzees experimentally superinfected with HDV. J Infect Dis 158:151-159.

Pisi E et al. 1987. Autoantibodies in chronic hepatitis delta virus infection. Prog Clin
Biol Res 234:249-256.

Polesky HF, Hanson MR. 1989. Transfusion-associated hepatitis C virus (non-A, non-B)
infection. Arch Pathol Lab Med 113:232-235.  [Published erratum appears in Arch
Pathol Lab Med 1989; 113(4):368]

Ponzetto A et al. 1987. Hepatitis delta virus infection in Pekin ducks chronically
infected by the duck hepatitis B virus. Prog Clin Biol Res 234:47-49.

Provost PJ et al. 1973. Etiologic relationship of marmoset-propagated CR326 hepatitis
A virus to hepatitis in man. Proc Soc Exp Biol Med 142:1257-1267.

Purcell R H et al. 1987. Experimental hepatitis delta virus infection in the chimpanzee.
Prog Clin Biol Res 234:27-36.

Rizzetto M, Verme G. 1985. Delta hepatitis--present status. J Hepatol 1:187-93.

Rizzetto M. 1989. Hepatitis delta virus (HDV) infection and disease. Ric Clin Lab
19:11-26.

Robbins SL, Cotran RS, Kumar V. Pathologic Basis of Disease, 3rd ed.; WB Saunders
Co., Philadelphia, 1984; pp. 900-910.

Robinson WS. 1979. Viruses of human hepatitis A and B. Comp Virol 14:471-526.
Scalise G et al. 1980. Transmission of hepatitis B to rhesus monkeys. J Med Primatol
7:114-118.

Scheuer PJ. 1989. Non-A, non-B hepatitis. Virchows Arch [A] 415:301-303.

Schulman AN et al. 1976. Hepatitis A antigen particles in liver, bile and stool of
chimpanzees. J Infect Dis 134:80.

Shao-Nan Huang L et al. 1979. Electron and immunoelectron microscopic study on liver
tissues of marmosets infected with hepatitis A virus. Lab Invest 41:63-71.

Shevtsova ZV et al. 1988. Spontaneous and experimental hepatitis A in Old World
monkeys. J Med Primatol 17:177-194.

Shouval D et al. 1980. Chronic hepatitis in chimpanzee carriers of hepatitis virus:
Morphologic, immunologic, and viral DNA studies. Proc Natl Acad Sci USA 77:6147-6151.

Slaughter RL. 1985. Viral infections of the liver. Ala J Med Sci 22:164-168.

Smith MS et al. 1980. Hepatitis A in nonhuman primates in nature (letter). Lancet
1(8206):1241-1242.

Tabor E et al. 1983. Primate animal models and titered inocula for the study of human
hepatitis A, hepatitis B, and non-A, non-B hepatitis.  Med Primatol 12:305-318.

Trahan CJ et al. 1987. Induced oral infection of the owl monkey (Aotus trivirgatus)
with hepatitis A virus. Lab Anim Sci 37:45-50.

Tsiquaye KN et al. 1984. Acute hepatitis A infection in hepatitis B chimpanzee carriers.
Hepatology 4:504-509.

Valenza FP, Muchmore E. 1985. The clinical chemistry of chimpanzees. II. Gamma
glutamyl transferase levels in hepatitis studies. J Med Primatol 14:305-315.

Zuckerman AJ et al. 1978. Hepatitis B outbreak among chimpanzees at the London Zoo.
Lancet 2:652-654.

Zuckerman AJ. 1978. The three types of human viral hepatitis. Bull WHO 56:1-20.


                                  Rift Valley Fever

      A hepatitis of man and other animals enzootic in many areas of Africa.  Nonhuman
primates may constitute reservoirs for human infection.  Agent is a Bunyavirus
(Bunyaviridae).

Cosgriff TM et al. 1989.  Hemostatic derangement produced by Rift Valley fever virus
in rhesus monkeys. Rev Infect Dis 11:(Suppl 4):S807-S814.

Johnson BK et al. 1982. Marburg, Ebola and Rift Valley Fever virus antibodies in East
African primates. Trans R Soc Trop Med Hyg 76:307-310.


                                    Poliomyelitis

1.    Agent:

      Human poliomyelitis viruses type 1, 2 and 3 - genus Enterovirus, family
Picornaviridae.

2.    Epizootiology:

      Macaques, African green monkeys, and Cebus spp. are susceptible to infection
but not to natural paralytic disease.  Naturally occurring paralytic disease, due to
infections probably acquired via human contact, has been reported in chimpanzees,
orangutans, gorillas, and colobus monkeys.

3.    Clinical:

      Fever, partial or complete flaccid paralysis of one or more limbs.

4.    Pathology:

      Classic lesion is poliomyelitis with degeneration and necrosis of anterior horn
cells.  Lesions can occur in other parts of spinal gray matter, brain stem, cerebellum,
and meninges.

5.    Diagnosis:

      Signs and lesions, virus isolation, serology.

6.    Control:

      Apes can be vaccinated with human polio vaccine.

7.    References:

Allmond BW et al. 1967. Paralytic poliomyelitis in large laboratory primates. Virologic
investigation and report on the use of oral poliomyelitis virus (OPV) vaccine.  Am J
Epidemiol 85:229-239.

Bodian D. 1972. Poliomyelitis.  In Pathology of the Nervous System, vol 3. Ed. Minckler
J, McGraw-Hill, New York, pp. 2323-2344.
Craig E et al. 1958. Contact transmission of poliomyelitis among monkeys. Proc Soc Exp
Biol Med 99:325-329.

Douglas J et al. 1970. The incidence of polio virus in chimpanzees (Pan troglodytes).
Lab Anim Care 20:265-268.

Guilloud NB et al. 1966. Paralytic poliomyelitis in the gorilla and orangutan. J Am Phys
Ther A 46:516-518.

Guilloud NB et al. 1969. Paralytic poliomyelitis in laboratory primates. J Am Vet Med
Assoc 155:1190-1193.

Howe HA, Bodian D. 1948. Poliomyelitis in the cynomolgus monkey following oral
inoculation. Am J Hyg 48:99-106.

Howe HA, Bodian D. 1944. Poliomyelitis by accidental contagion in the chimpanzee. J
Exp Med 80:383-390.

Howe HA, Bodian D. 1941. Poliomyelitis in the chimpanzee: A clinical-pathological
study. Bull Johns Hopkins Hosp 69:149-181.

Paul JR. 1971. A History of Poliomyelitis. Yale University Press, New Haven.
 
Suleman MA et al. 1984. An outbreak of poliomyelitis caused by poliovirus type I in
captive black and white colobus monkeys (Colobus abyssinicus kikuyuensis) in
Kenya. Trans R Soc Trop Med Hyg 78:665-669.


                                    Papovaviridae

1.    Papillomatosis.

Hollander CF, Van Noord MJ. 1972. Focal epithelial hyperplasia: A virus-induced oral
mucosal lesion in the chimpanzee. Oral Surg Oral Med Oral Pathol 33:220-26.

Lucke B et al. 1950. Transmissible papilloma in monkeys (brown Cebus). Fed Proc
9:337.

Rangan SRS et al. 1980. Virus associated papillomas in colobus monkeys (Colobus
guereza). Lab Anim Sci 30:885-889.

Tate CL et al. 1973. Focal epithelial hyperplasia in the oral mucosa of a chimpanzee.
J Am Vet Med Assoc 163:619-621.

2.    SV40

      Usually inapparent in rhesus monkeys, the natural hosts; others are
susceptible.  Sarcomas and ependymomas in neonatal hamsters and mastomys.  Once
a contaminant of human polio vaccine.

Gerber P. 1967. Patterns of antibodies to SV40 in children following the last booster
with inactivated poliomyelitis vaccines. Proc Soc Exp Biol NY 121:303-307.

Holmberg CA et al. 1977. Isolation of simian virus 40 from rhesus monkeys with
spontaneous progressive multifocal leukoencephalopathy. J Infect Dis 136:593-596.

London WT et al. 1983. Hydrocephalus, seizures, and incoordination in rhesus
monkeys infected in utero with SV-40 virus (Abstract). Lab Anim Sci 33:482-483.

Sheffield W. 1980. Simian virus 40 associated fatal interstial pneumonia and renal
tubular necrosis in a rhesus monkey.  J Infect Dis 142:618-622.

3.    Progressive multifocal leukoencephalopathy (PML)

      A progressive neurologic disease originally described in human patients; also
thought to be caused by papovavirus in humans.

Gribble DH et al. 1975. Spontaneous progressive multifocal leukoencephalopathy (PML)
in macaques. Nature 254:602-604.

Holmberg CA et al. 1977. Isolation of simian virus 40 from rhesus monkeys with
spontaneous progressive multifocal leukoencephalopathy. J Infect Dis 136:593-596.

4.    Miscellaneous

Takemoto KK, Segawa K. 1983. A new monkey lymphotropic papovavirus:
Characterization of the virus and evidence of a related virus in humans. Prog Clin
Biol Res 10:587-596.

Takemoto KK et al. 1982. Biological and biochemical studies of African green monkey
lymphotropic papovavirus. J Virol 42:502-509.


                                      Rotavirus

      Reoviridae.  Many infections described, but disease rare; expect mostly in
neonates.

References:

Ashley CR et al. 1978. Rotavirus infections of apes. Lancet 2:477.

Hrdy B. 1982. Rotavirus antibodies in hanaman langurs (Presbytis entellus). J Med
Primatol 11:35-38.
Kalter SS et al. 1983. Infection of baboons (Papio cynocephalus) with rotavirus (SV-
11). Dev Biol Stand 53:257-261.

Kalter SS. 1979. Electron microscopic examination of primate feces for rotaviruses.
Lab Anim Sci 29:516-518.

Kalter SS et al. 1982. Rotavirus (SA 11) antibody in nonhuman primates. Lab Anim Sci
32:291-293.

Majer M et al. 1978. Diarrhea in newborn cynomologus monkeys infected with human
rotavirus. Infection 6:71-72.

Malherbe HH, Strickland-Cholmley M. 1967. Simian virus SA 11 and the related 0 agent.
Arch ges Virusforsch 22:235-245.

Mitchell J et al. 1977. Transmission of rotavirus gastroenteritis from children to a
monkey. Gut 18:156-160.

Soike KF et al. 1980. Susceptibility of nonhuman primate species to infection by simian
rotavirus SV-11. AmJ Vet Res 41:1098-1103.

Stuker G et al. 1979. Virus detection in monkeys with diarrhea: The association of
adenoviruses with diarrhea and the possible role of rotaviruses. Lab Anim Sci 29:610-
616.

Wyatt RG et al. 1976. Induction of diarrhea in colostrum-deprived newborn rhesus
monkeys with the human reovirus-like agent of infantile gastroenteritis. Arch Virol
50:17-27.

Wyatt RG et al. 1978. Experimental infection of chimpanzees with the Norwalk agent
of epidemic viral gastroenteritis. J Med Virol 2:89-96.


                                Encephalomyocarditis


      A cardiovirus (Picornaviridae).  Encephalomyocarditis virus can cause
necrotizing and interstitial myocarditis in gibbons and owl monkeys.  Rhesus
sometimes have encephalomyelitis and paralysis; may recover.  Worldwide
distribution, rats probably natural host.  Simian disease in North and South America
and Africa.

Lesions: Cardiac dilation, pericardial effusion, pulmonary edema,
pleural effusion.

Gainer JH 1967. Encephalomyocarditis virus infection in Florida. J Am Vet Med Assoc
151:421-425.
Helwig FC, Schmidt ECH. 1945. A filter-passing agent producing interstitial
myocarditis in anthropoid apes and small animals. Science 102:31-33.

Roca-Garcia M, Sanmartin-Barberi C. 1957. The isolation of encephalomyocarditis virus
from Aotus monkeys. Am J Trop Med 6:840-852.


                  Simian Acquired Immunodeficiency Syndrome (SAIDS)

1.    Historical:

      Human AIDS was first reported by CDC in 1981.  Simian AIDS-like conditions have
been recognized in New England, California, Washington, Oregon, and Delta Regional
Primate Research Centers.

2.    Cause:

      Retroviral, probably several different ones.

      The family Retroviridae is divided into three subfamilies.  The Oncovirinae
include three unnamed genera comprising the types B, C, and D viruses.  The
Spumavirinae (foamy viruses) include the single genus Spumavirus, and the
Lentivirinae (slow viruses) include the single genus Lentivirus.  Morphology and
gene organization are major criteria for classification.  Typical oncoviruses have a
more nearly round (eicosahedral) core than lentiviruses, which have a cylindrical or
bar-shaped core, although some type D viruses have an eccentric elongated core
intermediate between that of a typical oncovirus and that of a lentivirus.  The basic
distinction between types C and D viruses is that the core of type D particles forms
in the cytoplasm first, then migrates to the cell membrane where the viral envelope
forms and budding occurs.  The core of type C particles, on the other hand, forms as
the envelope assembles and budding occurs.  Size, growth characteristics, antigenic
relationships, nucleic acid homology, and host range also are used in various
classification schemes.

      Human AIDS is caused by HIV-1 (human immunodeficiency virus-1), a lentivirus. 
Synonyms include LAV (lymphadenopathy virus), and HTLV-III (human T-
lymphotropic virus-III).  HIV-2 (HTLV-IV), another human lentivirus, is found only
in west Africa.  It appears to be less pathogenic than HIV-1; most people from whom
it has been recovered were apparently healthy.  SAIDS also is associated with
retroviral infections, but information concerning the specific agent or agents
responsible is somewhat confused.  Lentiviruses have been isolated from macaques
with SAIDS at NERPRC, CRPRC, and WRPRC.  These agents are closely related
genetically and are now generally considered to cause SAIDS in macaques.  They
currently are designated SIVmac (simian immunodeficiency virus of macaques).  In
terms of sequence homology in gag and pol genes and in gene organization, SIVmac
viruses are more closely related to HIV-2 than to HIV-1.  Another simian lentivirus,
SIVsmm (STLV-III/Delta), is closely related to SIVmac and apparently is prevalent in
captive sooty mangabeys (Cercocebus atys).  No evidence of immunodeficiency disease
has been found in the mangabeys; however, macaques inoculated with lepromatous
material from sooty mangabeys developed combinations of lymphoma, CMV disease,
candidiasis, cryptosporidiosis, wasting, lymphoid atrophy, marrow hyperplasia,
amyloidosis, gastritis, hepatitis, and syncytia in the meninges, lung, liver, lymph
nodes, kidney, and gastrointestinal tract.  This appears to have been due to SIVsmm
infection in the macaques.

      Still another nonhuman primate lentivirus, SIVagm (STLV-IIIagm), has been
isolated from apparently healthy wild-caught African green monkeys, and serologic
evidence indicates that infection is common.  It has not been associated with disease. 
It cross-reacts serologically with HIV-1 and HIV-2, but based on sequence homologies
SIVagm viruses form a group distinct from HIV-1 viruses and from the HIV-
2/SIVmac/SIVsmm group.  An additional SIV has been found in mandrills (Papio sphinx),
but its prevalence and pathogenicity are unknown.

      Knowledge of the cause(s) of SAIDS is clouded by the isolation of type D
retroviruses from affected monkeys at NERPRC, CRPRC, WRPRC, and ORPRC.  The
relationships among these agents have not been clarified, and it is unclear whether
or not any of them can cause or contribute to SAIDS.  The New England type D agent
did not cause disease after experimental inoculation.  The California virus, which is
easily transmitted and which is reported to cause SAIDS-like disease experimentally,
is referred to as SRV-1 (simian retrovirus-1).  SRV-1 has antigenic similarities to
Mason-Pfizer monkey virus.  The Washington type D virus, which is antigenically
similar to SRV-1, is called SRV-2; it appears to cause a fibroblastic proliferative
disease affecting mostly the abdominal viscera and called retroperitoneal
fibromatosis.  The Oregon virus is reported to be serologically similar to, but
nonetheless distinct from, the California virus; its relationship to SRV-1 has not been
established.  Thus, there are at least 2, and possibly more, type D retroviruses that
have been associated with SAIDS in addition to the aforementioned lentiviruses.

3.    Epizootiology:

      SAIDS is most common in rhesus and other macaques.  Natural reservoir, mode
of transmission, incubation period, etc., are not fully understood.  It is possible that
lentiviruses that cause immunodeficiency diseases are derived from lentiviruses that
are not pathogenic in the natural host species.  However, up to 50% of the African
green monkeys in their native habitat (sub-Saharan Africa) have antibodies to SIVagm,
up to 80% of captive sooty mangabeys have titers to SIVsmm.  The widespread
occurrence of SIVs in these species without apparent adverse effects suggests a long
evolutionary relationship.  Macaques appear not to have SIV infections in the wild;
SIVmac is closely related to SIVsmm.  Simian immunodeficiency viruses replicate well in
cultured human T cells, and the area of Africa in which HIV-2 (closely related to
SIVsmm) is endemic corresponds to the range of sooty mangabeys.

      At CRPRC the California type D virus has been found in saliva and urine of a
healthy carrier, and infection was transmitted by inoculation of infected saliva.
4.    Clinical signs and laboratory results:

      Human AIDS is characterized by lymphoid depletion, depressed cellular and
humoral immunity, opportunistic infections, and neoplasms such as Kaposi's sarcoma
(endothelial origin) and lymphoma.  There usually is lymphopenia and decreased ratio
of T4+ (helper-inducer) lymphocytes to T8+ (suppressor-cytotoxic) lymphocytes. 
Human patients usually have normal or increased immunoglobulins.  Some patients
have CNS signs.

      Signs of SAIDS are not specific and usually are related to secondary infectious
conditions.  M. cyclopis at NERPRC in 1980-81 had anemia, neutropenia, bizarre
circulating mononuclear cells, increased hepatic enzymes, decreased serum albumin,
hypogammaglobulinemia, wasting, diarrhea, lymphoma, and diseases such
pneumocystosis or noma.  Responses of their lymphocytes to mitogens and mixed
lymphocyte culture were decreased, but their lymphocyte counts and T4/T8 ratios
were normal.

      Rhesus monkeys from which SIV was isolated did, however, have decreased
numbers of T4+ lymphocytes.  Naturally infected monkeys had lymphoma,
opportunistic infections, or both.  Monkeys inoculated with lymphoma tissue or plasma
died rapidly with conditions such as candidiasis, generalized cytomegalovirus
disease, cryptosporidiosis, intestinal trichomoniasis, and encephalitis.

      At the California RPRC, 42 rhesus monkeys were found to have lymphoma and
concurrent progressive multifocal leukoencephalopathy or disease due to M. avium-
intracellulare or Herpesvirus simiae from 1965-1975.  A second outbreak began in 1976
in stumptailed macaques, and featured high mortality with encephalitis, oral
candidiasis, and enteric mycobacteriosis (M. avium).  In 1976-1981, a third outbreak
affected rhesus monkeys and was characterized by generalized lymphadenopathy,
severe anemia and lymphopenia, secondary bacterial infections, and high mortality. 
A fourth outbreak began in 1981 and continues at present.

      At the Washington center, SAIDS has affected primarily pigtail macaques but also
other species of macaques.  These animals had persistent diarrhea, progressive
weight loss, anemia, lymphopenia, opportunistic infections, and a high incidence of
retroperitoneal fibromatosis, a neoplasm-like condition whose cells bear some
similarities to those of Kaposi's sarcoma.

      The ORPRC retrospectively recognized a SAIDS-like condition seen as early as
1978 in Celebes black macaques and rhesus monkeys.  These animals had weight loss,
diarrhea, anemia, lymphopenia, lymphadenopathy, splenomegaly, hypoproteinemia, and
retroperitoneal fibromatosis.

5.    Pathology:

      Lesions related specifically to SAIDS include lymphoid hyperplasia followed by
progressive depletion.  Some monkeys have had lymphoproliferative lesions such as
infiltrates in liver, kidney, and bone marrow, or outright lymphosarcoma. 
Encephalitis similar to that occurring in human AIDS (perivascular granulomatous
inflammation with multinucleated giant cells) occurs in some cases.  Other lesions
result from infections with CMV, SV40, Pneumocystis carinii, mycobacteria,
Cryptosporidium, Candida, and other agents.

      The pathogenesis of the disease still is unclear; however, the California group
has reported that monkeys dying of fulminant SAIDS after inoculation with SRV-1 had
much circulating virus and did not have detectable antibody responses to the virus. 
Monkeys that developed a milder form of the disease had chronic mild viremia, and
those that did not develop signs of SAIDS had no or transient viremia and high
concentrations of antibody against the virus.  Chakrabarti et al (1987) report that
SIV causes disease more similar to human AIDS in that it also is tropic for
lymphocytes of the T helper phenotype.

6.    Diagnosis: serologic techniques, such as indirect IFA and ELISA; immunoblotting;
virus isolation & identification

7.    Control:

      Isolation.  May be difficult because of long incubation period, and best measures
not really known because transmission not fully understood.

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                                 Other Retroviruses

1.    Type C oncornaviruses

      (i) Endogenous.  Integral part of genome, transmitted genetically.  Low virus
      production, low infectivity, usually no disease in natural host species but may
      cause natural or experimental disease in other species.

      Examples:

           (a) Baboon endogenous virus

           (b) Macaca arctoides C type virus

           (c) Owl monkey endogenous C type virus

           (d) Colobus polykomos C type virus

           (e) Macaca mulatta C type virus

           (f) "Fetoplacental type C particles" seen in Old World primates (baboon,
           rhesus, chimp, patas, cynomolgus), New World primates (marmoset,
           capuchin), and prosimians (tree shrews)

           (g)"New World monkey type C particles" seen in howler (Alouatta sp.) and
           capuchin.

      (ii) Exogenous.  Not genetically transmitted, but infectious and horizontally
      transmitted; potential cause of disease.

           Examples:

           (i) Simian sarcoma virus (helper) and simian sarcoma-associated virus
           (defective), isolated from a woolly monkey (Lagothrix sp.) with
           fibrosarcomas.  Fibrosarcomas and gliomas in marmosets.

           (ii) Gibbon ape leukemia-lymphosarcoma virus, isolated from gibbons with
           hematopoietic neoplasms.  Experimentally reproducible, but unknown
           whether natural disease in wild.

2.    Type D oncornaviruses

      (i) Endogenous

           (a) Squirrel monkey retrovirus (squirrel monkey endogenous virus). 
           Broad host range including man, rhesus, nonprimate mammals.  No
           transformation in vitro.

           (b) Langur endogenous virus.

      (ii) Exogenous

           (i) Mason-Pfizer monkey virus.  Isolated from mammary cancer in rhesus. 
           Little or no tumorigenic activity demonstrable, but is pathogenic for infant
           rhesus.  Three patterns observed: thymic atrophy and immuno-
           suppression with runting, increased susceptibility to pneumonia and
           enteritis, death; erythrocytic basophilia with or without anemia, death; and
           neutropenia with or without anemia, most survived.

3.    References

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Benveniste RE et al. 1974. Detection of baboon type C viral sequences in various
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Bryant ML, Sherr CJ, Sen A et al. 1978. Molecular diversity among five different
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Chopra HC. 1976. An oncorna-type virus from monkey breast tumor. Prog Med Virol
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Chopra HC, Mason MM. 1970. A new virus in a spontaneous mammary tumor of a rhesus
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Colcher D, Termato YA, Schlom J. 1977. Interspecies radioimmunoassay for the major
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Deinhart F. 1980. Biology of primate retroviruses. In Viral Oncology, ed. Klein, Raven
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DePaoli A. 1973. Granulocytic leukemia in whitehanded gibbons. J Am Vet Med Assoc
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Donehower L et al. 1977. Divergence of baboon endogenous type C virogene in
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Feldman D. 1975. An electron microscopic study of virus particles in rhesus monkey
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Heberling RL et al. 1977. Oncornavirus: Isolation from a squirrel monkey lung culture.
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Heberling RL et al. 1976. Isolation and biological properties of endogenous baboon
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Hino S, Tronick SR, Heberling RL et al. 1977. Endogenous New World primate
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Johnson PB. 1974. Studies on simian foamy viruses and syncytium forming viruses of
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Kalter SS et al. 1975. Brief communication: C-type viruses in chimpanzee placentas.
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Kalter SS et al. 1975. C-type particles in baboon placenta. Proc Royal Soc Med 68:135-
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Kawakami TG et al. 1972. C-type virus associated with gibbon lymphosarcoma. Nature
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Nemo GJ. 1978. Antigenic relationship of human foamy virus to the simian foamy
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Neubauer RH et al. 1974. Attempts to demonstrate type C virus in normal and
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Parks WP et al. 1973. Radioimmunoassay of mammalian type C polypeptides. In
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Prowten AW et al. 1985. T-cell lymphoma associated with immunologic evidence of
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Richardson JH et al. 1971. Rabies in imported nonhuman primates. Lab Anim Sci
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Sasagawa A et al. 1981. Absence of antibodies against SV5, measles and herpes simplex
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Stuker G et al. 1979. Virus detection in monkeys with diarrhea: The association of
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???.

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Suzuki M. 1981. Natural virus infections in cynomolgus monkeys. Jap J Med Sci Biol
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Tauraso NM. 1973. Review of recent epizootics in nonhuman primate colonies and their
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Valerio A. 1971. Colony management as applied to disease control with mention of some
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