Inhibition of human immunodeficiency virus (HIV-1) replication in vitro 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. Significant 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 microM 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 uninfected cells. These results with CPT suggest that this compound may represent a new class of drugs with antiretroviral potential.
Priel
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Department of Microbiology & Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
Showalter
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Blair
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D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology*; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D014779:Virus Replication / Q000187:drug effects*
D059004:Topoisomerase I Inhibitors; D012194:RNA-Directed DNA Polymerase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin