We had previously described a novel topoisomerase I (topo I) activity associated with two strains of HIV, equine infectious anemia virus (EIAV) and Moloney murine leukemia virus. This observation suggested that topo I could play a role in the retroviral life cycle, so we tested whether topoisomerase inhibitors could interfere with the retroviral life cycle. We have examined the ability of the topoisomerase I inhibitor, camptothecin (CPT), to inhibit retrovirus infection. We observed that non-cytotoxic doses of CPT, if present at the time of viral infection, reduce the level of virus infection by about 90% as measured by both reverse transcriptase and p24 expression at 7 days post-infection. In contrast, two topoisomerase II inhibitors had no effect on HIV infection and growth. CPT does not block the ability of reverse transcriptase to utilize an exogenous template, suggesting the inhibition may act at some other stage in the viral life cycle.
