RESTRICTION AND ENHANCEMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION BY MODULATION OF INTRACELLULAR DEOXYNUCLEOSIDE TRIPHOSPHATE POOLS

Human immunodeficiency virus type 1 (HTV-1) replication is shown to be sensitive to the intracellular concentration of deoxynucleoside triphosphate substrates. Addition of thymidine to established cell lines resulted in a dramatic reduction of virus production. The effect could be substantially alleviated by addition of deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3. Hydroxyurea treatment abolished HIV-I replication in peripheral blood mononuclear cells and could be reversed by deoxyadenosine. These data show that HIV-1 replication occurs under suboptimal DNA precursor conditions.