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A new serotype of simian acquired immune deficiency syndrome (SAIDS) retrovirus (type 2) belonging to the D genus of retroviruses is associated with a SAIDS occurring spontaneously in a colony of Celebes macaques (Macaca nigra) and rhesus macaques (Macaca mulatta) at the Oregon Regional Primate Research Center. This syndrome resembles SAIDS in M. mulatta at the California Primate Research Center, which is associated with a similar type D retrovirus (type 1). However, at the Oregon Center, SAIDS is distinguished by the occurrence of retroperitoneal fibromatosis in some of the affected monkeys. Type 2 virus was isolated from seven of seven macaques with SAIDS, retroperitoneal fibromatosis, or both and from one of six healthy macaques. The new strain is closely related to SAIDS retrovirus type 1 and Mason-Pfizer monkey virus but can be distinguished by competitive radioimmunoassay for minor core (p10) antigen and by genomic restriction endonuclease cleavage patterns. Neutralization tests indicate that type 1 and type 2 SAIDS retroviruses are distinct serotypes. Therefore, separate vaccines may be necessary to control these infections in colonies of captive macaques.

Type D retrovirus was isolated from rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) and transmitted to healthy rhesus macaques with tissue culture medium containing the virus. The clinical, immunologic, and lymph node morphologic changes were observed in 9 rhesus macaques for 52 weeks after inoculation. A spectrum of clinical signs developed including early death, persistent SAIDS, and apparent remission. Animals that died or developed persistent SAIDS had characteristic lymphoid depletion, persistently depressed peripheral blood mononuclear cell (PBMC) mitogenic response, and decreased serum immunoglobulins. The SAIDS retrovirus (SRV) was recovered from PBMC of 8 of the animals after inoculation. Virus could not be recovered from PBMC of one animal in remission, but this animal developed serum-neutralizing antibodies to SRV after inoculation. Seven of the animals seroconverted to SRV after inoculation, all 9 were seronegative for human T-lymphotropic virus-III, and 5 animals tested were seronegative to human T-lymphotropic virus-I. These findings support the etiologic role of the type D retrovirus in SAIDS and further define the pathogenesis of this disease.

Two rotavirus strains isolated in cell culture from infant rhesus monkeys with diarrhea were closely related to SA 11 virus and to each other by plaque reduction neutralization tests. However, results of immune electron microscopy suggested possible antigenic differences between the two rhesus rotavirus strains.

Benign and malignant lesions from monkeys were analyzed for the presence of papillomavirus (PV) DNA. By hybridization with different PV DNA probes under conditions of lowered stringency, two tumors were found to contain PV-specific DNA sequences: (1) a cutaneous papilloma from a Colobus monkey; and, (2) a lymph node metastasis of a squamous cell carcinoma of the penis from a Rhesus monkey. Analysis of the DNA of the papilloma from the Colobus monkey indicated the presence of extrachromosomal DNA whereas analysis of DNA from the Rhesus tumor suggested the presence of integrated viral DNA. The physical size (7.8 and 8.1 kb), colinear alignment to HPV-5, and cross-hybridization with other PV types under low stringency indicate that the two genomic DNA clones represent new PV types that have been tentatively designated as Rhesus papillomavirus type 1 (RhPV 1) and Colobus guereza papillomavirus type 2 (CgPV 2). A putative viral-host DNA junction fragment was also isolated from the Rhesus genomic library. Nucleotide sequences very closely related to RhPV 1 were observed by in situ hybridization in a laryngeal carcinoma from the Colobus guereza monkey. This report communicates the finding of novel papillomaviruses associated with a benign cutaneous tumor and genital and laryngeal malignancies in non-human primates which may have significance as a putative system for the study of papillomavirus-induced genital and laryngeal malignancies in humans.

The objectives of tests for extraneous agents will be discussed in the light of quality requirements for biological products published over the last twenty years, current developments of novel production methods and products, and past and current virological findings.

Simian acquired immune deficiency syndrome (SAIDS) in the macaque genus of monkeys at the California Primate Research Center is apparently caused by infection by a type D retrovirus. The complete nucleotide sequence (8173 base pairs) of a molecular clone of the prototype SAIDS virus isolate, SRV-1, reveals a typical retrovirus structure with long terminal repeats (346 base pairs) and open reading frames for the gag (663 codons), pol (867 codons), and env (605 codons) genes. SRV-1 also has a separate open reading frame of 314 codons between the gag and pol genes that defines the viral protease gene (prt) and a short open reading frame of unknown significance downstream from the env gene. The SRV-1 protease region shows a high degree of homology to its counterpart in the hamster intracisternal A-type particle genome; both these protease genes are about twice as long as the analogous region of other retroviruses. SRV-1 has no notable similarity in either genetic organization or sequence to the human AIDS retroviruses.

22 monkeys were randomly allocated to one or other of 2 communes and fed a caries-promoting high sucrose diet. After 28 weeks commune 1 (13 monkeys) was found to harbour Streptococcus mutans serotype e as the predominant streptococcal species, but no monkey in commune 2 harboured this serotype. Instead the 9 monkeys of commune 2 harboured Streptococcus milleri in their dental plaque. The significance of these observations on the use of monkeys as a model of human dental caries is discussed.

Acquired immuno-deficiency syndrome (AIDS) of macaques, an animal model for human AIDS, was transmitted to previously healthy macaque monkeys by means of inoculation of either tissue or a cell-free filtrate of a macaque lymphoma. The recipients showed evidence of profound lymphocyte dysfunction or died with infections from such opportunistic agents as Candida albicans, Cryptosporidium, and cytomegalovirus.

The predominant cultivable bacteria in the supra-gingival plaque of Old World monkeys were similar to those in human plaque. A significant interanimal species difference was observed in the absolute and relative concentration of specific microbial populations. Streptococcus mutans serotype c was found primarily in rhesus plaque and serotype e in cynomolgus plaque.

The isolation of a T-cell tropic retrovirus from three immunodeficient macaques and one macaque with lymphoma is described. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of acquired immune deficiency syndrome in humans (HTLV-III or LAV). This virus is referred to as simian T-lymphotropic virus type III (STLV-III) of macaques. The existence of a cytopathic, T-cell tropic virus resembling HTLV-III in monkeys may facilitate study of disease induction and vaccine development in an animal model.

We have isolated a biologically active molecular clone of simian immunodeficiency virus (SIV), SIVmac 1A11, originally obtained from a rhesus macaque at the New England Regional Primate Research Center. Virus derived from cells transfected with this clone is cytopathic for rhesus peripheral blood mononuclear cells, replicates in cultures of rhesus macrophages, and infects rhesus macaques when inoculated intravenously. Six macaques inoculated with SIVmac 1A11 all became infected and produced antibodies to viral envelope glycoproteins that neutralized virus. Antibodies to viral core proteins were detected in only one animal. No clinical signs of disease were observed throughout 7 months postinoculation.

The results of adaptation of hepatitis A viral strain JaM-55 to the culture of embryo kidney cells FRhk-4 from macaque Rhesus are presented. The viral strain was isolated from a M. fascicularis suffering from spontaneous hepatitis. Before inoculating the cell culture the virus was passaged twice in the M. arctoides capable of reproducing hepatitis. FRhk-4 cell line inoculation by the monkey liver extract, containing the strain HAV-YaM-55, resulted in isolation of single viral particles of hepatitis A in the preparations obtained at the first 3 passages by the 28-31 day of cultivation. Beginning from the fourth passage the abrupt increase in the number of viral particles and hepatitis A antigen was registered. There were no traces of cytopathogenic effect at any level of viral passages in the inoculated cell culture. The adapted virus contains hepatitis A viral RNA identified by spot hybridization with the cloned cDNA of hepatitis A virus.

Core polypeptides of primate lymphotropic retroviruses (PLRV) have very similar molecular weights. To discriminate between individual PLRVs we have compared two-dimensional tryptic peptide maps of 125I-labeled core polypeptides p19 and p24 of 11 isolates originating from humans and six simian species. Peptide maps showed homologies between all the simian viruses and the human isolates, but they were completely different from those of human T-cell leukemia virus type III (HTLV-III). In general p24s are more conserved than p19s. According to the relationship of their peptide maps we have classified the PLRVs into three groups, the human and chimpanzee isolates, macaque viruses, and green monkey virus.

Stump-tailed macaque virus, a newly recognized papovavirus of the SV40 polyoma subgroup, was demonstrated in kidney cultures from each of five stump-tailed macaque fetuses in the second half of gestation and from six adult stump-tailed macaques. Such regular presence of virus in the fetus is an unusual feature for a papovavirus.

Examination of chorionic villi from rhesus monkey placenta revealed the presence of C-type virus particles budding from syncytial trophoblast, pericytes, Hofbauer cells, and mesenchyme. In addition, particles, were found budding from cells of the cytotrophoblastic cell column and decidual basalis. They measured 30 nm in diameter, had a dense central core, surrounded by a narrow, electron-lucent zone, and were enclosed by an outer unit membrane.

At the University of Washington Regional Primate Research Center, a simian acquired immunodeficiency syndrome (SAIDS) associated with retroperitoneal fibromatosis (RF) has been observed in 82 macaques since 1976, including 77 pigtailed macaques (Macaca nemestrina), two long-tailed macaques (M. fascicularis), one Japanese macaque (M. fuscata) and two rhesus macaques (M. mulatta). The syndrome is characterized by immunodeficiency accompanied by a fibroproliferative lesion, primarily affects young monkeys (1-3 years) and has a high case fatality rate. Based on the occurrence of RF in colony-born and non-colony-born monkeys, the minimum incubation period for natural exposure is believed to be about 9 months. The incidence of RF was 0.9% in M. nemestrina, 0.1% in M. fascicularis, 1.0% in M. fuscata and 0.4% in M. mulatta. There were no significant differences in the incidence of RF by sex or seasonality. Epidemiologic studies were focused on 42 juvenile M. nemestrina that developed RF between January 1980 and June 1983, and the results were compared with 42 age- and sex-matched controls. The incidence of RF was 5.7% in monkeys 12-24 months old and 3.4% in monkeys 24-36 months old, but less than 1.0% in age groups of under 1 year and over 3 years. No significant associations were found for housing history, parentage, generations or ancestral origins. Epidemiologic information and preliminary viral studies suggest a type D retrovirus may be the causative agent in RF and SAIDS. RF associated with SAIDS appears to be an excellent model for Kaposi's sarcoma associated with human AIDS.

A type C retrovirus was isolated from a continuous cell line established from a spontaneous esophageal carcinoma of a rhesus monkey (Macaca mulata) by prolonged cocultivation with canine cells. A DNA transcript of the viral RNA hybridized to a high level and kinetic analysis indicated the presence of multiple copies of the viral genome in rhesus monkey DNA, showing that the virus is endogenous in this species. The rhesus monkey virus closely resembles, in several respects, an endogenous type C virus previously isolated from stumptailed macques (Macaca arctoides), aa species closely related to rhesus monkeys.

The result of the complement fixation (CF) test for the antibody to herpes simplex virus (HSV) in sera of the cynomolgus monkeys was compared with that of the neutralization test (NS) for the antibody to herpes B virus (HBV) in the same sera. Fifty-seven (74%) of 77 wild-originated monkeys were positive for HSV-CF, while 65 (84%) of the 77 animals were positive for HBV-SN. All of the 57 CF positive cases were also positive for HBV-SN. On the other hand, 30 (75%) of 40 laboratory-bred monkeys had neither HSV-CF antibody nor HBV-SN antibody. Remaining 10 of the 40 laboratory-bred animals were positive for HSV-CF. However, no HBV-SN antibody was detected in nine of the 10 HSV-CF positive animals. These results suggest that the HSV-CF test may be as satisfactory as the HSV-SN test as a practical measure for rough screening of HBV infection in the cynomolgus monkey in laboratories having no containment unit for handling HBV.

Intraocular granulomas associated with tuberculosis were observed in 2 subhuman primates (Ateles geoffroyi and Macaca mulatta). Bacterial cultures from lung tissues at the time of necropsy confirmed the presence of Mycobacterium bovis and M tuberculosis, respectively. The absence of generalized clinical signs in spite of systemic dissemination of the organisms in these cases and the public health significance of tuberculous infections emphasize the importance of proper observation and diagnostic procedures in primate colonies and display collections.

Fatal herpesvirus infections were diagnosed in 3 patas monkeys and 1 black and white colobus monkey over a 4-week period. Herpesvirus was isolated from 1 patas monkey and from the black and white colobus monkey. Both isolates had growth characteristics similar to Herpesvirus hominis and Herpesvirus simiae. The isolate from the colobus monkey antigenically appeared to be H simiae or H simiae-like, whereas the isolate from the patas monkey could not be conclusively identified with the antisera used. All affected animals were housed in close proximity to rhesus monkeys, the carrier host of H simiae.

A rhesus monkey with a naturally acquired STLV-III infection developed immunosuppression and a lymphoproliferative syndrome characterized by progressive lymphadenopathy and widespread visceral mononuclear cell infiltration. On microscopic examination, diffuse sheets of plasmacytoid lymphoblasts obliterated the sinuses and follicles of the nodes, replaced normal cellular elements of the spleen, bone marrow, and thymus, and infiltrated the lung, liver, kidney, salivary gland, pancreas, thyroid, stomach, and tongue. Immunohistologic studies indicated that the predominant cell in these infiltrates was a B lymphocyte, of oligo- or polyclonal origin. Similar but less extreme lymphoproliferative abnormalities were seen at necropsy in a substantial number of other animals with naturally occurring macaque immunodeficiency syndrome. The present case represents the first prospectively studied monkey with a naturally acquired simian T lymphotropic virus type III infection and illustrates an important manifestation of disease associated with such an infection.

We have studied the serological relationship among the human immunodeficiency virus type 1 (HIV-1), and three simian immunodeficiency viruses (SIV). SIVagm was isolated from African green monkeys (Cercopithecus aethiops), and compared with the previously described isolates of SIVmac from a rhesus macaque (Macaca mulatta) and SIVsm from a sooty mangabey (Cercocebus atys). With respect to the glycoproteins, the simian viruses represent a subgroup apparently different from HIV. To classify HIV and SIV isolates further, we compared tryptic peptide maps of the core polypeptides p 18 and p 24 of HIV-2, three HIV-1 and five SIV isolates. Each peptide map was distinguishable, and differences are most prominent between the HIV-1 group and the SIVmac/SIVsm group. HIV-2 is very similar to SIVmac and SIVsm. The three SIVagm isolates form a more heterogeneous group. The p24s of all SIVagms are more similar to the p24s of HIV-1, but with respect to p 18, one isolate is similar to HIV-1, while the two others are more related to SIVmac, SIVsm, and HIV-2.

Saccharomyces cerevisiae, an ascomycetous yeast and a candidate for a host-vector system in recombinant DNA experiments, was examined for its pathogenicity and colonization in mice and cynomolgus monkeys as the models of the biological containment level. Adult mice given perorally with 5.5 or 2.4X10(7) cells of MC16 strain S. cerevisiae excluded them rapidly and no colonization of the cells in the abdominal organs, lymph nodes or gastrointestinal wall was demonstrated. No change in the fecal flora was observed. Cynomolgus monkeys after peroral administration of 4.9X10(7) or 7.8X10(8) cells showed a similar tendency of rapid exclusion and the lack of colonization. Cortisone acetate treatment had no significant effect. Intravenous administration of 3.9X10(7) yeast cells had no pathogenic effect and no viable yeast cell was detected in the blood. The biological containment level of S. cerevisiae was suggested to be not lower than that of E. coli K12 B1 level, and the possibility of achieving the B2 level was also suggested.

Celebes macaques were tested for type D simian retrovirus (SRV) infection. SRV infection was first detected in one serum sample collected during 1980. By 1983, 32 of 46 monkeys (70%) were infected. Serotyping of the SRV isolates determined that 0/26 of the isolates were SRV-1; 24/26 were SRV-2; 1/26 was SRV-5; and 1/26 could not be typed. Restriction endonuclease mapping confirmed the SRV-2C and SRV-5 isolates. In addition, two SRV-2C variants were detected.

Stool specimens collected systematically from a group of Celebes black macaques (Macaca nigra) with a high incidence of diarrhea were examined microbiologically. Numerous isolates of Shigella flexneri, Campylobacter jejuni and pathogenic Escherichia coli were recovered. Previous parasitology reports had revealed that the majority of the animals had Balantidium coli. Subsequently, the group was treated with trimethoprim-sulfamethoxazole, erythromycin and tetracycline. After treatment, Shigella flexneri was not detected in the stool of any animal for 1 year, and the clinical condition of the group was improved. Reduced recovery rates were obtained with other enteric pathogens.

Ultrastructures of Japanese monkey (Macaca fuscata)-derived type C virus particles in a monkey lymphoid cell line, expressing adult T-cell leukemia (ATL)-associated antigens, are indistinguishable from those of human ATL-associated virus in human and monkey cell lines.

Simian acquired immunodeficiency syndrome (SAIDS) was transmitted to four of four rhesus macaques with blood from rhesus macaques naturally infected with a type D retrovirus, simian retrovirus-2 (SRV-2). Three of the four blood recipients died with SAIDS at 13, 15, and 26 weeks postinoculation. The fourth animal is alive with SAIDS. All four test monkeys became viremic and produced antiviral antibody. None of the inoculated monkeys produced measureable neutralizing antibody to SRV-2. The survivor produced higher levels of antiviral antibody than the monkeys that died. Phytohemagglutinin and concanavalin A reactivity of peripheral blood lymphocytes was depressed from weeks 6 to 12 after inoculation. Clinical findings included development of splenomegaly in all four monkeys, and diarrhea in two monkeys. Blood counts remained within the normal range except for a depression in the number of polymorphonuclear lymphocytes in two monkeys. Hematocrits were decreased in two monkeys just prior to their death. All four test monkeys developed lymph node atrophy and bone marrow hypoplasia. Total proteins and immunoglobulin production were normal. This report provides evidence that SRV-2, as well as other type D retroviruses, causes SAIDS in macaque species.

Sixty-seven Macaca rhesus monkeys were inoculated with 2 mutants and 3 virulent strains of tick-borne encephalitis (TBE) virus including strains isolated from patients with a chronic form of TBE. A model of the clinical course of acute, subacute, and chronic encephalitis was produced by intracerebral inoculation and that of asymptomatic infection was produced by subcutaneous inoculation [with or without administration of cyclophosphane (CP)]. Virus persistence developed after inoculation with all the strains, after non-fatal encephalitis and inapparent infection irrespective of CP administration. In monkeys recovering from encephalitis the virus persisted for at least 783 days. After asymptomatic infection, it persisted for 302 days; neither virus nor virus-specific antigen was detected at 356, 367, and 620 days.

Twenty three strains of simian viruses isolated from nasopharyngeal swabs and respiratory tissues of cynomolgus monkeys showing mild symptoms of respiratory disorders were classified into three groups by their biological, serological and morphological characteristics. Thirteen strains classified as group 1 were judged to be enteroviruses. Four strains of group 2 and six strains of group 3 were identified as simian adenoviruses. Yields of the ten simian adenoviruses of groups 2 and 3 were compared in three continuous cell lines after several serial passages.

The occurrence of foamy viruses among baboons and macaca monkeys in Sukhumi monkey farm was investigate;. The monkeys were shown to be carriers mainly of foamy virus type II. The frequency of virus isolation increased with the age of the animals and reached 88.8-100% in adult specimens. The virus behaviour in cell cultures is described. The morphological characteristics of the virus are based on electron microscopic examinations of ultrathin sections of primary and inoculated cell cultures.