9-nitrocamptothecin selectively inhibits human immunodeficiency virus type1 replication in freshly infected parental but not 9-nitrocamptothecin-resistant U937 monocytoid cells

We have previously reported that 9-nitrocamptothecin (9NC) inhibited human immunodeficiency type 1 (HIV-1) replication in latently HIV-l-infected T ly mphocytic ACH-2 cells stimulated with the cytokine tumor necrosis factor al pha (TNF-alpha) (Moulton et al,, AIDS Res Hum Retroviruses 1998;14:39), 9NC induced an accelerated apoptosis in HIV-l-infected, but not uninfected, ly mphocytic cells, The present study demonstrates that 9NC selectively inhibi ts release of HIV-1 from freshly infected monocytoid U937 cells in a dose-r esponse manner. Significant inhibition was achieved with concentrations of 9NC that were not toxic. In contrast, HIV-1 replication in 9NC-resistant mo nocytoid cells, derived from U937, was not inhibited by similar doses of 9N C, Importantly, sensitivity of HIV-1 replication to 9NC correlated with the effect of 9NC on topoisomerase I (topo I) activity. In a 9NC-sensitive sub line, 9NC induced posttranslational activation of the nuclear transcription factor kappa B (NF-kappa B) after the drug treatment. This activation was neither related to selective 9NC suppression of HIV-1 replication, nor was it sufficient for the 9NC-induced toxicity in the drug-sensitive monocytoid cells. Taken together, the selective inhibition of HIV-1 replication in bo th lymphoid and monocytoid cells lends further credence to the potential de velopment of 9NC as an alternative drug for treating HIV-1 infection.