Search

A type D retrovirus related to but distinct from Mason-Pfizer monkey virus was isolated in vitro from the blood of two rhesus monkeys (Macaca mulatta) with simian acquired immunodeficiency syndrome (SAIDS). Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks.

A neurotropic retrovirus causes a naturally occurring lower-limb paralysis in wild mice, characterized by a noninflammatory spongiform change located primarily in the lower spinal cord. The causative agent is an ecotropic murine leukemia virus, unique to certain wild mice in southern California. The disease is readily transmitted to newborn susceptible laboratory mice. The paralytogenic property is attributed to direct viral injury to motor neurons and glial cells and is associated with unique amino acids in the murine leukemia virus envelope gp70. This murine model may have relevance to both human T-lymphotropic virus type I, and human immunodeficiency virus infection of human brain. It presents a practical model for testing antiviral agents aimed at retrovirus infection of the mammalian central nervous system. Simian acquired immunodeficiency syndrome type D retrovirus causes a silent infection of the brain in infected macaques. Viral nucleic acids are detected in the brain parenchyma in the absence of viral antigen, neurological symptoms, and neuropathology. Infected choroid plexus epithelial cells are the source of cell-free virus in the cerebrospinal fluid of viremic monkeys. This model adds yet another example of retroviral infection of the central nervous system and points to the choroid plexus as a potential source of infectious virus.

Seventeen isolates of retrovirus D/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was prepared from Hirt supernatants of cells infected with one of these isolates (D/New England 398). By restriction endonuclease analysis, cloned pD398 DNA represented full-length viral DNA with one long terminal repeat. A detailed restriction endonuclease map of pD398 was derived and compared with a map of the cloned Mason-Pfizer monkey virus genome. Forty-six percent (13 of 28) of restriction endonuclease sites were found to be conserved when these related viruses were compared. Five of the D/New England isolates, including those from three different macaque species, were examined for strain variability by restriction endonuclease typing. Comparison of over 30 restriction endonuclease sites has not distinguished any of these D/New England isolates. It thus appears that a single strain of type D retrovirus is infecting three different species of macaques in the New England colony. Markedly reduced cross-hybridization was observed between cloned pD398 and Mason-Pfizer monkey virus DNAs at high stringency; this reduced cross-hybridization was localized to the pol-env regions of the genome. Only very weak hybridization of D/New England DNA to cloned squirrel monkey type D retrovirus DNA could be detected even at low-stringency conditions. What role type D retrovirus plays in the immunodeficiency syndrome of macaques remains to be determined.

The nucleotide sequences of the long terminal repeat (LTR) of simian retroviruses (STLV), which are closely related to human T-cell leukemia virus type I (HTLV-I) were found to be of at least two subgroups: an Asian subtype in macaques and an African subtype in African green monkeys and chimpanzee. The nucleotide sequence of HTLV-I was found to be included within the divergence among STLV, but showed closer homology (95%) to African subtype STLV than to Asian subtype STLV (90%).

Information on the extent of genetic variability among non-human primate lentiviruses related to human immunodeficiency virus (HIV) is sorely lacking. Here we describe the isolation of two molecular clones from the simian immunodeficiency virus (SIV) and their use to derive restriction endonuclease maps of five SIV isolates from rhesus macaques and one from a cynomolgus macaque. Although similar, all six viral isolates are readily distinguishable; the single isolate from a cynomolgus macaque is the most different. The restriction endonuclease map of one macaque isolate (SIVMAC-251) is identical to that published by others for STLV-IIIAGM of African green monkeys and for HTLV-IV of humans. Nucleotide sequences from the envelope region of cloned SIVMAC-251 have more than 99% identify to previously published sequences for STLV-IIIAGM (refs 2, 4) and HTLV-IV (ref. 4). These results and other observations provide strong evidence that isolates previously referred to as STLV-IIIAGM and HTLV-IV by others are not authentic, but were derived from cell cultures infected with SIVMAC-251.

Cell cultures established from the spleen of a Macaca nemestrina with enzootic retroperitoneal fibromatosis (ERF) spontaneously released a unique retrovirus. Throughout 14 serial passages, the spleen cell cultures remained fibroblastic and no cytopathic effect was evident. The virus incorporates [3H]uridine, contains an RNA-dependent DNA polymerase (RDDP), has a buoyant density of 1.15 g/cm3 in sucrose, and was designated MNV-1. Virion-associated reverse transcriptase showed no preference for either Mg2+ or Mn2+ in standard RDDP assays. Complementary DNA (cDNA) transcribed from polyadenylated MNV-1 RNA hybridized to genomic DNA and RNA extracted from diseased tissues but not to nucleic acids from normal tissues of a healthy Macaca nemestrina or a Macaca mulatta. MNV-1 is therefore exogenous to these species. MNV-1 had no detectable homology to the endogenous macaque virus isolates MAC-1 and MMC-1. Liquid hybridization of MNV-1 cDNA to viral RNA derived from exogenous and endogenous subhuman primate retroviruses (SiSV(SSAV), GALV-SF, BaEV-M7, and BILN) did not reveal any significant sequence homologies. In addition, MNV-1 does not share homology with bovine leukemia virus or Mason-Pfizer monkey virus as determined by Southern blot hybridization. We conclude that MNV-1 is a unique retrovirus which has not previously been described. As the ultrastructure of virions in in vitro cell cultures, as well as disease involved tissue, show some particles with type C morphology and others with type D morphology, MNV-1 may be comprised of more than one component.

The major core protein (p28) of MMC-1, an endogenous type C virus of the rhesus monkey (Macaca mulatta), was purified and subjected to structural and immunological analyses. The NH2-terminal amino acid sequence of MMC-1 p28 showed extensive homology to the sequences of the major structural proteins (p30) of known mammalian type C viruses. Similarly, interspecies antigenic determinants shared by all the above viral proteins were detected in MMC-1 p28. Competition radioimmunoassays together with the results of statistical analysis of the primary structure data provided evidence that MMC-1 p28 is not more closely related to primate type C viruses of the Papio genus than to those isolated from rodents, cats, or New World monkeys. MMC-1 p28 was found to be closely related structurally to the p30 protein of the avian reticuloendotheliosis virus (REV-A), a horizontally transmitted type C virus of putative mammalian origin. In addition, MMC-1 p28 and REV-A p30 shared a specific subset of antigenic determinants not present in any of the other avian or mammalian type C viruses studied. These findings suggest that MMC-1 and REV may have a common evolutionary origin.

A total of 703 sera from 10 species of monkeys were examined for the presence of antibodies to adult T-cell leukemia (ATL)-associated antigens (ATLA). ATLA represent core protein(s) of ATL virus (ATLV) and ATLV-determined polypeptides. Anti-ATLA antibodies were found in all seven macaque species tested but not in three non-macaque species. The frequencies of seropositive macaques ranged from 10 to 50%. In three macaque species (Japanese monkeys, rhesus monkeys, and crab-eating monkeys) in which sufficient numbers of animals were studied, more females than males were anti-ATLA positive and the antibody-positive rate increased with age. In Japanese monkeys, over 70% were seropositive after the age of 10 years. A family study of Japanese monkeys suggested maternal transmission of ATLV or a closely related agent. These seroepidemiological features are consistent with those of Japanese in the ATL-endemic area. Three of 10 rhesus monkeys were found to be anti-ATLA-positive 13 days after arrival in Japan, suggesting that they had been infected with ATLV in Indonesia where they were captured. Thus, ATLV appears to be prevalent among several macaque species as well as in man, and its pathogenetic role in these non-human primates should be explored in relation to ATL in man.

Comparison of Mason-Pfizer monkey virus and squirrel monkey retrovirus (both candidate type D oncornaviruses) by immunoelectron microscopy revealed that these two viruses do not share common surface antigens.

Because of the growing incidence of AIDS (acquired immune deficiency syndrome), the need for studies on animal models is urgent. Infection of chimpanzees with the retroviral agent of human AIDS, the human immunodeficiency virus (HIV), will have only limited usefulness because chimpanzees are in short supply and do not develop the disease. Among non-human primates, both type D retroviruses and lentiviruses can be responsible for immune deficiencies. The D-type retroviruses, although important pathogens in macaque monkey colonies, are not satisfactory as a model because they differ in genetic structure and pathophysiological properties from the human AIDS viruses. The simian lentivirus, previously referred to as simian T-cell lymphotropic virus type III (STLV-III), now termed simian immunodeficiency virus (SIV) is related to HIV by the antigenicity of its proteins and in its main biological properties, such as cytopathic effect and tropism for CD4-bearing cells. Most importantly, SIV induces a disease with remarkable similarity to human AIDS in the common rhesus macaques, which therefore constitute the best animal model currently available. Natural or experimental infection of other monkeys such as African green monkeys or sooty mangabeys has not yet been associated with disease. Molecular approaches of the SIV system will be needed for biological studies and development of vaccines that could be tested in animals. We have cloned and sequenced the complete genome of SIV isolated from a naturally infected macaque that died of AIDS. This SIVMAC appears genetically close to the agent of AIDS in West Africa, HIV-2, but the divergence of the sequences of SIV and HIV-2 is greater than that previously observed between HIV-1 isolates.

Infectious retrovirus(es) associated with the human (LAV, HTLV-III, ARV) and simian (SAIDS-1) acquired immune deficiency syndrome were compared by electron microscopy, immunofluorescence and immunoblotting techniques and by restriction endonuclease mapping of the viral genomes. The extracellular virus particles had similar type D morphology, but intracytoplasmic type A nucleoids were found only in SAIDS virus infected cells. Although the antigens of the three prototype AIDS viruses were similar, no cross-reactivity with the SAIDS virus was detected. Molecular hybridization and restriction enzyme analysis also revealed that the SAIDS and AIDS viruses were genetically unrelated. However, only minor differences, consistent with strain polymorphism, were found between the three AIDS virus isolates. Thus, the retroviruses associated with AIDS in macaques and humans are unique to each species.

A primate lymphotropic lentivirus was isolated on the human T-cell line HuT 78 after cocultivation of a lymph node from a pig-tailed macaque (Macaca nemestrina) that had died with malignant lymphoma. This isolate, originally designated M. nemestrina immunodeficiency virus (MnIV) and now classified as simian immunodeficiency virus (SIV/Mne), was inoculated intravenously into three juvenile rhesus monkeys (Macaca mulatta), three juvenile pig-tailed macaques (M. nemestrina), and two juvenile baboons (Papio cynocephalus). All six macaques became viremic by 3 weeks after inoculation, whereas neither of the baboons developed viremia. One pig-tailed macaque died at 15 weeks with suppurative peritonitis secondary to ulcerative, necrotizing colitis. Immunologic abnormalities included a marked decrease in CD4+ peripheral blood lymphocytes. Although five macaques mounted an antibody response to SIV/Mne, the animal that died at 15 weeks remained antibody negative. Three other macaques (two rhesus and one pig-tailed) died 66 to 87 weeks after inoculation after exhibiting progressive weight loss, anemia, and diarrhea. Histopathologic findings at necropsy included various manifestations of immune deficiency, nephropathy, subacute encephalitis, pancreatitis, adenocarcinoma, and lymphoid atrophy. SIV/Mne could be readily isolated from the spleens and lymph nodes of all necropsied macaques, and from the cerebrospinal fluid, brains, bone marrow, livers, and pancreas of some of the animals. SIV antigens were localized by avidin-biotin immunohistochemistry to pancreatic islet cells and to bone marrow endothelial cells. The data suggest that African baboons may be resistant to infection by SIV/Mne, whereas Asian macaques are susceptible to infection with this pathogenic primate lentivirus.

Horizontally acquired SAIDS retrovirus type 2 (SRV-2), a type D retrovirus related to the Mason-Pfizer monkey virus, has been associated with the simian acquired immunodeficiency syndrome (SAIDS) including retroperitoneal fibromatosis (RF) in several macaque species at two primate research centers. Virus specific gene sequences are present in lymphoid and RF tissues but not in muscle tissue of diseased macaques or in any tissues of uninfected normal monkeys. Serologic and restriction endonuclease mapping techniques have defined unique SRV-2 strains in the Celebes (SRV-2C) and rhesus (SRV-2R) macaques at the Oregon Regional Primate Center, SRV-2 is related to both MPMV and SAIDS type 1 retroviruses and it has no detectable molecular homology with the human AIDS retroviruses.

An examination of various rhesus monkey (Macaca mulatta) organs has shown a preference for type C viral antigen expression in the placenta. Separate cocultivations of isolated trophoblasts from 10 rhesus monkey placentas with cell lines from heterologous mammalian species led to rapid isolation of type C rhesus retrovirus in 4 of 10 cases. These four retrovirus isolates have been designated MMC-2 through MMC-5. Five of the remaining six sets of cocultivations grew simian foamy virus and were discontinued. Distinction of these viral isolates from the initial rhesus isolate (MMC-1) and the previous isolate from the stumptail monkey, Macaca arctoides (MAC-1), could be made by liquid DNA hybridization, although not by limited restriction endonuclease digestion. Both MAC-1 and MMC-1 were obtained in single long-term cocultivation experiments (over 7 months). The present isolates MMC-2 through MMC-5 were detected in 2 to 5 weeks. Consequently, primary trophoblast cells represent a useful differentiated cell type for isolation of infectious retrovirus from this primate species.

A provirus clone of simian T-cell leukemia virus isolated from a pigtailed monkey (PT-STLV), which is 90% homologous to HTLV-I, was shown to be biologically active in transfection assay. In transfected cells, gp61env, Pr55gag, and the mature gag proteins p24, p21, and p15 were detected, and type C particles were produced. The virus could be transmitted from the transfectants to recipient cells by cocultivation. In this biologically active provirus clone, a coding frame, possibly for protease, was identified between the gag and pol genes. The corrected sequence of the protease region of HTLV-I was also found to have a single open reading frame overlapping the gag and pol genes, although it has an amber codon in the middle of the frame. Thus, a single coding frame, which is different from those of gag and pol, is common to proteases of the HTLV family including HTLV-I.

C-type virus particles and particles, approximately 35 nm in diameter, were present in the region of the basal plate from the placenta of a rhesus monkey and two baboons. Both particles appeared to bud from the plasma membrane of the cytotrophoblast: large, pleomorphic cells with cytoplasmic extensions, indented nuclei, well-developed endoplasmic reticulum, and glycogen deposits. Extracellular particles were enmeshed within a fibrous matrix. Particles were also observed in the junctional zone, but not in the decidua. C-type virus particles from the rhesus monkey and baboons differed in ultrastructure from each other and from C-type mouse leukemia virus particles. The 35-nm-type particle was spherical with a dense central core.

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.

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.

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.

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.

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.

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.

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.

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.

The type D subfamily of retroviruses contains five distinct viruses which are found in New and Old World monkeys. The retroviruses found in Old World macaque (genus Macaca) monkeys are exogenous to the species and upon injection induce a fatal simian acquired immune deficiency syndrome (SAIDS). Two serotypes of type D virus, SAIDS retrovirus types 1 and 2 (SRV-1 and SRV-2), are found in captive macaques in primate centres in the United States. In addition to SAIDS, two neoplasms, retroperitoneal fibromatosis (RF) and subcutaneous fibrosarcomas (SF), have been found in macaques with type D retrovirus-induced SAIDS. Only SRV-2 is found in association with RF, and only about 35% of SRV-2-infected macaques develop RF. SF is found in association with both serotypes, but less than 5% of infected monkeys develop SF. The RF in macaques is potentially a model for human disease since the lesions in macaques are similar to the idiopathic RF described in humans. Thus far, RF has not been found in species other than macaque or man. The complete sequence of three type D retroviruses is known. Importantly, no oncogenes are present in the viral genome. Therefore, the mechanisms for tumour induction which involve immunosuppressive or genetic properties of the virus that are distinct from classic oncogenes must be considered.

Type D retroviruses have recently been shown to induce a wasting syndrome with associated lymphadenopathy, thymic atrophy and transient decreased peripheral blood lymphocyte blastogenic responsiveness in juvenile macaque monkeys. The replication in vitro of D/New England virus was assessed in various lymphocyte subpopulations to determine the possible pathogenesis of the immune dysfunction induced by this virus. While D/New England did not replicate in cultured T lymphocytes or induce any demonstrable dysfunction of T cells in vitro, it did grow in the cells of the B lymphocyte lineage. D/New England growth occurred in vitro in African Burkitt's lymphoma and pre-B cell lines, but not in Epstein-Barr virus-transformed normal B lymphocytes. The infection of a restricted B lymphocyte population by this primate type D retrovirus may play a role in the aetiology of the immune abnormalities which it induces.

Human T-lymphotropic virus type III (HTLV-III) is thought to play an etiologic role in the development of the acquired immune deficiency syndrome (AIDS). In this study the serologic characterization of a new simian retrovirus that is related to HTLV-III is described. This new virus, here referred to as STLV-III, was isolated from sick macaques at the New England Regional Primate Research Center. Radioimmunoprecipitation analysis revealed STLV-III-specific proteins of 160, 120, 55, and 24 kilodaltons, all similar in size to the major gag and env proteins of HTLV-III. These antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-III, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with the macaque virus. This HTLV-III-related virus, which naturally infects a nonhuman primate species, may provide a useful model for the study of HTLV-III and the pathogenesis of AIDS.

A new class of endogenous primate type C virus has been isolated from a continuous tissue culture line of Macaca arctoides cells by co-cultivation with a human cell line. The virus, designated MAC-1, can be transmitted to human and feline cells in tissue culture, and is unrelated, by immunological and nucleic acid hybridization criteria, to previously characterized retroviral isolates of primates. In particular, MAC-1 shows no detectable homology to the baboon type C viruses, even though viral genes related to the latter group are readily detected in M. arctoides cellular DNA. Viral gene sequences related to the MAC-1 genome are present in multiple copies (50-150 per haploid genome) in Old World primates, and are expressed in the cellular RNAs of uninfected and "virus-free" primate cells and tissues. Thus there are at least two distinct sets of genetically transmitted Old World primate type C viral genes, each of which is found in multiple copies in normal primate cellular DNA. With the description of this new retrovirus, there are now a minimum of five distinct genetically transmitted viruses of primates, three type C and type D, each represented in multiple copies in the normal cellular DNA.