Adult T-cell leukemia-like disease in monkey naturally infected with simian retrovirus related to human T-cell leukemia virus type I.
Hajime TsujimotoMotoharu SeikiHideo NakamuraToshiki WatanabeIppei SakakibaraAkira SasagawaShigeo HonjoMasanori HayamiMitsuaki Yoshida
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Abstract:
Spontaneous T-cell leukemia similar to human adult T-cell leukemia (ATL) was found in an African green monkey naturally infected with simian retrovirus closely related to human T-cell leukemia virus type I (HTLV-I). Monoclonal integration of the simian retrovirus was detected in the primary leukemic cells, suggesting an association of the retrovirus with ATL-like leukemia in the monkey.Keywords:
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African Green Monkey
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Sixteen isolates of simian retrovirus closely related to human immunodeficiency virus (HIV) were obtained from healthy African green monkeys (AGM) (Cercopithecus aethiops). The first isolate was obtained from a monkey seropositive for HIV, and the others were isolated from monkeys harboring antibodies to the first isolate. These simian retroviruses were referred to as simian immunodeficiency virus from AGM, SIV[AGM], due to their cross-reactivities with HIV structural proteins. These SIV[AGM] isolates were found by Western blotting analysis to have virus-specific proteins of 120, 66, 55, 32-40, 24 and 17 kDa, which were all similar in size to the analogous proteins of HIV. Putative gag proteins of p55, p24 and p17 were recognized by sera of human AIDS patients, but the corresponding env proteins of 32-40 and 120 kDa showed only weak cross-reactivity with those of HIV. The transmembrane glycoproteins of these 3 SIV[AGM] isolates showed size heterogeneity, being 32, 35 and 40 kDa. This virus had particles that were morphologically similar to those of HIV, and had Mg2+-dependent reverse transcriptase. Furthermore, the SIV[AGM] showed tropism and cytopathic effects on CD4-positive human cell lines. In a sero-epidemiological survey of SIV[AGM] in various non-human primates, 2 other African monkey species, the mandrill and de Brazza's monkey, were also found to have antibodies to SIV[AGM]. These HIV-related simian retroviruses will be important in determining the origin and transmission of HIV group viruses, and may provide useful animal models for studies on the infection and pathogenesis of HIV and AIDS.
Simian
Simian immunodeficiency virus
African Green Monkey
Cercopithecus aethiops
Hylobates
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Deltaretrovirus
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The type C retrovirus simian T-lymphotropic virus type III (STLV-III) has been isolated recently from immunodeficient macaque monkeys at the New England Regional Primate Research Center. The present studies were done to define the in vitro growth characteristics of this agent. STLV-III replicates efficiently in interleukin 2-dependent T-cell cultures of macaque peripheral blood lymphocytes (PBL), less efficiently in such cultures of human and gibbon PBL, and inefficiently in baboon PBL. No replication, as assessed by measuring reverse transcriptase activity in these culture supernatants, could be detected in similarly maintained cultures of chimpanzee, squirrel monkey, and cotton-top tamarin PBL. Like the human acquired immunodeficiency syndrome (AIDS) virus, human T-cell lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV), STLV-III replicates in T4+ but not T8+ lymphocytes and its infection of macaque and human lymphocytes can be blocked with monoclonal anti-T4 antibodies. STLV-III differs from the human AIDS virus, however, in its apparent inability to grow in the Epstein-Barr virus-transformed B lymphocytes tested, the differing range of nonhuman primate T-cell populations that support its growth, and its less striking toxicity for T lymphocytes. These studies provide further characterization of an agent that will be extremely important in facilitating the development of vaccines and antiviral therapy for AIDS.
African Green Monkey
Simian
Cercopithecus aethiops
Simian immunodeficiency virus
Human T-lymphotropic virus
Rhesus macaque
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Human T-cell leukemia virus type I (HTLV-I) is exogenous for human transmission by viral infection and was shown to be a causative agent of adult T-cell leukemia (ATL) in man. Monkeys of several species were found to have antibodies reactive with HTLV-I antigens and thus infection with HTLV-I like retroviruses was suspected. The retroviruses in several species of monkeys were characterized by Southern hybridization, molecular cloning and sequencing. These monkey retroviruses, tentatively called simian T-cell leukemia viruses (STLV), have a genome structure of LTR-gag-pol-env-pX-LTR and are highly homologous with HTLV-I in all regions. A DNA clone of the STLV was isolated from a pig-tailed monkey and the nucleotide sequence was determined. The STLV showed 90% homology in the nucleotide sequence with that of HTLV-I in env-pX-LTR region. This highly homologous sequence indicates that the STLV is a member of the HTLV family but apparently different from HTLV-I. This result excluded the possibility of recent interspecies viral transmission from monkeys to humans, and suggested that STLV can be useful as an animal model in studies on HTLV-I transmission and leukemogenesis in humans. Supporting this suggestion, an African green monkey which was naturally infected with STLV was found to have developed T-cell leukemia that was very similar to human ATL.
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African Green Monkey
Simian immunodeficiency virus
Bovine leukemia virus
Deltaretrovirus
clone (Java method)
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African Green Monkey
Simian immunodeficiency virus
Simian
Rhesus macaque
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Spontaneous T-cell leukemia similar to human adult T-cell leukemia (ATL) was found in an African green monkey naturally infected with simian retrovirus closely related to human T-cell leukemia virus type I (HTLV-I). Monoclonal integration of the simian retrovirus was detected in the primary leukemic cells, suggesting an association of the retrovirus with ATL-like leukemia in the monkey.
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African Green Monkey
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Proviral integration of a simian retrovirus highly homologous to human T-cell leukemia virus type I was examined in cellular DNAs extracted from primary peripheral blood lymphocytes of 31 adult African green monkeys (Cercopithecus aethiops) that were seropositive for simian T-cell leukemia virus type I (STLV-I). Among these monkeys, one case with overt leukemia, showing pleomorphic leukemia cells similar to those in human adult T-cell leukemia (ATL), and five cases in a preleukemic state of ATL-like disease were found. Judging from the integration site of the provirus genome, primary lymphocytes of these leukemic or preleukemic cases contained monoclonally proliferated STLV-I-infected cells, whereas lymphocytes of other seropositive monkeys without hematological abnormalities were polyclonal, and those of seronegative monkeys did not contain the provirus. The restriction patterns with PstI ans SstI of most STLV-I proviruses were identical to those of the previous isolate from this species, but in three monkeys there was a deletion of one PstI site. From the correlation of the development of simian ATL-like disease with the monoclonal integration of the STLV-I provirus genome, it should be indicated that STLV-I has similar leukemogenicity to human T-cell leukemia virus type I, and so STLV-I infection in African green monkeys will be useful as an animal model of human ATL.
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African Green Monkey
Simian
Oncovirus
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