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Studies of Genetic Variation in the AIDS Virus: Relevance to Disease Pathogenesis, Anti-Viral Therapy, and Vaccine Development

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Annual rept. 15 Dec 1987-14 Dec 1988

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Genetic and biologic studies of Human Immunodeficiency Virus Type 1 HIV-1 aimed at developing an understanding of disease pathogenesis, viral evolution, and methods to treat and prevent infection have expanded to include study of the closely related human and simian immunodeficiency viruses. In our DoD funded work, we are pursuing the contract study aims by molecular analyses of HIV-1 and HIV-2, with focus on four primary aims i nature and extend of genetic variation, ii mechanism and rate of viral variation, iii influence of host immune response on variation, and iv effect of genetic variation on viral antigenicity, immunogenecity, and biology. In this annual report, we summarize results and conclusions obtained in the past year year 02 in the areas of HIV- 1 variation in vivo and genetic and biologic analysis of HIV-2. In these studies, we have demonstrated for the first time that HIV-1 exists as a quasispecies, that genetic variation of HIV-1 develops in parallel with common viral forms persisting over time, and that changes in nucleotide and amino acid sequences accumulate in the envelope immunodominant loop region. In addition, recent clinical and seroepidemiological studies in West Africa indicate that HIV-2 is widespread and associated with immunodeficiency states of variable degree. In this study, a T-lymphotropic human retrovirus, HIV-2ST, representing the first bone fide isolate of HIV-2 from Senegal was molecularly cloned and characterized in regard to its biologic and structural properties and its genetic relatedness to known primate retroviruses. Keywords RA 1 AIDS HTLV- III Virology HIX Restriction maps Genetic maps.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Biology
  • Microbiology

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