INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV-1) REPLICATION INVITRO BY NONCYTOTOXIC DOSES OF CAMPTOTHECIN, A TOPOISOMERASE-I INHIBITOR

We examined the effects of topoisomerase inhibitors on human immunodeficiency virus type 1 (HIV-1) infection of H9 cells in cell culture. Infection is blocked or substantially reduced by the topoisomerase I inhibitor camptothecin (CPT), but not by two topoisomerase II inhibitors. Significantly reduction (greater-than-or-equal-to 90%) in the amount of virus released, as measured by reverse transcriptase, is obtained if the cells are treated for 1 h with 0.01-0.02-mu-M CPT at the time of virus infection, and expression of viral proteins is also blocked. CPT is also shown to reduce the level of infection when chronically infected cells are cocultivated with unifected cells. These results with CPT suggest that this compound may represent a new class of drugs with antiretroviral potential.