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A highly divergent simian immunodeficiency virus (SIVstm) recovered from stored stump-tailed macaque tissues.

ABSTRACT: We report here the results of molecular analysis of a simian immunodeficiency virus (designated SIVstm) which was isolated from a rhesus monkey inoculated with stored lymph node tissue of an Asian stump-tailed macaque. The latter monkey had died in 1977 during an epidemic of acquired immunodeficiency and lymphoma at the California Regional Primate Research Center (L. J. Lowenstine, N. W. Lerche, P. A. Marx, M. B. Gardner, and N. C. Pedersen, p. 174-176, in M. Girard and L. Valette, ed., Retroviruses of Human AIDS and Related Animal Viruses, 1988). Nucleotide sequence analysis of the gag and env regions indicates that SIVstm is an ancient member of the SIV/human immunodeficiency virus type 2 group; it is quite divergent from known SIVs isolated from African sooty mangabeys as well as from Asian macaques. Furthermore, of all SIV strains described to date, SIVstm is the most closely related to human immunodeficiency virus type 2.

SUBMITTER: Khan AS

PROVIDER: S-EPMC250828 | biostudies-other | 1991 Dec

REPOSITORIES: biostudies-other

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A highly divergent simian immunodeficiency virus (SIVstm) recovered from stored stump-tailed macaque tissues.

Khan A S AS Galvin T A TA Lowenstine L J LJ Jennings M B MB Gardner M B MB Buckler C E CE

Journal of virology 19911201 12

We report here the results of molecular analysis of a simian immunodeficiency virus (designated SIVstm) which was isolated from a rhesus monkey inoculated with stored lymph node tissue of an Asian stump-tailed macaque. The latter monkey had died in 1977 during an epidemic of acquired immunodeficiency and lymphoma at the California Regional Primate Research Center (L. J. Lowenstine, N. W. Lerche, P. A. Marx, M. B. Gardner, and N. C. Pedersen, p. 174-176, in M. Girard and L. Valette, ed., Retrovir ...[more]

PMID: 1942258

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Project description:The influence of major histocompatibility complex class I (MHC-I) alleles on human immunodeficiency virus (HIV) diversity in humans has been well characterized at the population level. MHC-I alleles likely affect viral diversity in the simian immunodeficiency virus (SIV)-infected pig-tailed macaque (Macaca nemestrina) model, but this is poorly characterized. We studied the evolution of SIV in pig-tailed macaques with a range of MHC-I haplotypes. SIV(mac251) genomes were amplified from the plasma of 44 pig-tailed macaques infected with SIV(mac251) at 4 to 10 months after infection and characterized by Illumina deep sequencing. MHC-I typing was performed on cellular RNA using Roche/454 pyrosequencing. MHC-I haplotypes and viral sequence polymorphisms at both individual mutations and groups of mutations spanning 10-amino-acid segments were linked using in-house bioinformatics pipelines, since cytotoxic T lymphocyte (CTL) escape can occur at different amino acids within the same epitope in different animals. The approach successfully identified 6 known CTL escape mutations within 3 Mane-A1*084-restricted epitopes. The approach also identified over 70 new SIV polymorphisms linked to a variety of MHC-I haplotypes. Using functional CD8 T cell assays, we confirmed that one of these associations, a Mane-B028 haplotype-linked mutation in Nef, corresponded to a CTL epitope. We also identified mutations associated with the Mane-B017 haplotype that were previously described to be CTL epitopes restricted by Mamu-B*017:01 in rhesus macaques. This detailed study of pig-tailed macaque MHC-I genetics and SIV polymorphisms will enable a refined level of analysis for future vaccine design and strategies for treatment of HIV infection.Cytotoxic T lymphocytes select for virus escape mutants of HIV and SIV, and this limits the effectiveness of vaccines and immunotherapies against these viruses. Patterns of immune escape variants are similar in HIV type 1-infected human subjects that share the same MHC-I genes, but this has not been studied for SIV infection of macaques. By studying SIV sequence diversity in 44 MHC-typed SIV-infected pigtail macaques, we defined over 70 sites within SIV where mutations were common in macaques sharing particular MHC-I genes. Further, pigtail macaques sharing nearly identical MHC-I genes with rhesus macaques responded to the same CTL epitope and forced immune escape. This allows many reagents developed to study rhesus macaques to also be used to study pigtail macaques. Overall, our study defines sites of immune escape in SIV in pigtailed macaques, and this enables a more refined level of analysis of future vaccine design and strategies for treatment of HIV infection.

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A highly divergent simian immunodeficiency virus (SIVstm) recovered from stored stump-tailed macaque tissues.

Publications

A highly divergent simian immunodeficiency virus (SIVstm) recovered from stored stump-tailed macaque tissues.

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