CELLULAR PATHWAYS INVOLVED IN VIRAL INDUCTION--THEIR ROLE IN HIV PATHOGENESIS

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Induction of HIV from a latent state was studied using the U1 cell line. Specifically, the effect of various chemical carcinogens and environmental mutagens was examined for their ability to induce virus from this cell line with the objective of identifying risk factors of physiologic relevance that may affect disease progression in AIDS. U1 cells were treated with 2 different concentrations of various carcinogens. Virus production was measured by p24 antigen, RT, DNA and RNA analysis. Enhances virus production was seen in cells treated with benzopyrene, NNK and aflatoxin B. Viral induction was accompanied by an increase in NF-KB activity and production of cytokines such as TNF-alpha. In the case of aflatoxin, virus induction appeared to be a TNF-a independent mechanism. The role of other cytokines, second messengers and cellular signaling pathways in the induction of HIV by these agents is currently under investigation. These experiments are also being performed in chronically infected cells that produce low levels of virus.