Although it is well established that HIV is the primary T-cell pathogen in the development of AIDS, the variable attack rate, the high incidence of concurrent infections with other viruses, and evidence that herpes viruses and HIV may act synergistically in vitro, suggest that other viral copathogens may be important in the development of AIDS. Furthermore, AIDS patients have a high incidence of Epstein-Barr virus (EBV)-associated B-cell lymphomas, most frequently of the Burkitt type. It has also been shown that only B-cells infected with EBV can be infected with HIV. All of these findings suggest that interactions between EBV and HIV may be important in the pathogenesis of AIDS and AIDS- related lymphoma. We will prospectively study parameters of EBV infection (viral serology, viral shedding, and EBV-transformed peripheral blood lymphocytes) in a cohort of HIV-positive patients who are well and will correlate any observed changes in these parameters with the development of AIDS. We will undertake a detailed study of AIDS-related lymphoma. In this analysis we will determine clonality by immunoglobulin gene rearrangement analysis. EBV genome copy number, EBV strain subtype, and the expression of candidate EBV transforming genes (EBNA2 and LMP), as well as EBV transcriptional activator genes. EBV-positive cells from various sources will be infected with HIV. These paired HIV+ and HIV- B-cell lines will be used to determine the effect of HIV on B-cell interleukin 2 receptor expression, immunoglobulin production, EBV gene expression, and clonagenicity of infected cells. These cells will also be used to determine the effect of a resident EBV genome on HIV expression.
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