SYNERGY BETWEEN EBV AND HIV 1 DURING LYMPHOGENESIS

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The host cell range for Epstein-Barr virus (EBV) is now known to be much broader than originally believed and now includes, in addition to B cells and epithelial cells, some types of T cells. It has been proposed that accelerated disease progression might occur when the same individual is coinfected with both HIV-1 and EBV and synergy between EBV and HIV-1 has been suggested. Previously we have shown that overlapping host cell range resulted in altered HIV-1 expression and EBV-induced transformation in coinfected peripheral blood lymphocytes (PBLs) and PBL subpopulations. We have also detected synergy between the IIIB strain of HIV-1 and EBV during infection of homogeneous population of CD19+ B cells. Many aspects of pathology associated with uncontrolled EBV replication are manifested during HIV-1 infection. Conventional thought is that the elevated levels of EBV expression are the direct result of reduced T cell surveillance. Uncontrolled EBV is essential for EBV-associated lymphomas to develop. The specific aim of this proposal is to use established techniques in a novel approach to determine whether direct synergy between EBV and HIV-1 occurs in vivo. Specifically, we will use quantitative polymerase chain reaction (PCR) and virus rescue to detect EBV expression and measure HIV-1 load in CD3+, CD4+. CD8+, CD19+ and monocytes/macrophages from normal EBV-seropositive individuals and patients infected with HIV-1-positive individuals with and without lymphoma. The lymphoma group will be subdivided into EBV-associated with non-EBV-associated. The second study group will consist of individuals newly diagnosed as HIV-1 who have chosen intervention with standard antiretroviral therapy with and without anti-herpes virus therapy. Both groups will be studied longitudinally, with the specific aims of (i) determining whether lymphoma development can be correlated with viral burden in particular lymphocyte subpopulations, and (ii) determining the effects of antiretroviral therapy with or without anti-herpes virus therapy on viral burden in lymphocyte subpopulations.