Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection share similar epidemiologic features; moreover both viruses require reverse transcription for replication. During studies to examine the possible role played by HBV in the development of AIDS, two extrachromosomal 3.2kb DNAs hybridizing to HBV DNA were cloned from the peripheral blood mononuclear cell (PBMC) DNAs of HIV infected patients. One of the clones appears to be typical HBV DNA; however the other clone hybridized to both HBV and HIV DNA probes. A major objective of this proposal is to survey the various populations of HIV-infected patients in our medical school complex, especially those patients in the various ACTU protocols, for the presence of HBV-related sequences in PBMCs. We want to determine whether correlations exist between the presence of HBV-related DNA with stage of the HIV infection; the numbers of CD4+ cells; the clinical course of the HIV infection; the presence of neurologic disease; the presence of various opportunistic infections; the presence of various neoplasias; the response to the various therapies, including those of the ACTG protocols; and the isolation of HIV strains resistant to the various therapeutic agents such as AZT, ddC and ddI. Experiments will be performed to determine whether the HBV-related DNA is cell associated or found in the supernatants of the PBMC cultures of HIV-infected patients, in the free state or in particulate forms. PBMCs containing the HBV-related DNA will be examined for the location of the DNA, whether cytoplasmic or intranuclear; the expression of HBV antigens; and the expression of HBV and HIV-HBV homologous transcripts. The cellular subtype that harbors the HBV-recombinant DNA, whether T4, T8 or non-T cell will be determined. Experiments will be performed to examine the effect of HIV on the replication of HBV DNA in PBMCs and H9 cells. The major questions to be addressed by these studies are: 1) can data be garnered to implicate HBV as a cofactor in the progression of HIV infection to AIDS; 2) does the presence of HBV DNA in the PBMCs affect the clinical course of HIV infection including the response to treatment; 3) does treatment of HIV infection with nucleoside analogues affect the presence of HBV DNA in the PBMCs; 4) does HIV facilitate the replication of HBV DNA in mononuclear cells; and 5) what are the correlates of the presence of apparent HIV-HBV recombinant DNA molecules in PBMCs of HIV-infected patients and what are some of the molecular characteristics of the replication of this apparent recombinant molecule in PBMCs and H9 cells?

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Mount Sinai School of Medicine
New York
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