DETECTION AND SIGNIFICANCE OF SI VARIANTS OF HIV

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HIV, the virus that causes AIDS, evolves rapidly in each human host and the sequence variability in HIV is important for disease progression. The long-term objectives of this proposal are to examine the significance and consequences of sequence variability in HIV. One example of this variability is the syncytium-inducing (SI) class of HIV-1 that can form syncytia in T lymphocytes in vitro and evolves de novo in 50 percent of HIV-1 infected individuals. As a first specific aim for this proposal, recombinant viruses will be constructed using patient viral sequences to test their in vitro phenotypes. The sequences to be used have been identified by a V3-specific heteroduplex tracking assay as evolutionary variants that do not have the SI phenotype. The relationship between the sequences and their phenotypes will provide insight into the correlation between SI phenotype and disease progression. The second aim is to isolate SI and non-SI sequences from specific patients. The sequences will be used as probes for in situ hybridization of lymphoid tissue from the same patients to examine the distribution of the variants in lymphoid tissue. Other aims involve the determination of the correlation between the presence of evolutionary variants in plasma with: 1) the evolution toward the SI phenotype, 2) rapid disease progression, and 3) antiretroviral drug therapy failure. The V3-specific heteroduplex tracking assay will be used in all of these experiments to detect the presence of V3 evolutionary variants in circulating virus.