9-Nitrocamptothecin inhibits HIV-1 replication in human peripheral blood lymphocytes: A potential alternative for HIV-Infection/AIDS therapy

被引:13
作者
Hung, CL
Doniger, J
Palini, A
Snyder, SW
Radonovich, MF
Brady, JN
Pantazis, P
Sadaie, MR
机构
[1] NovoMed Pharmaceut Inc, Germantown, MD 20875 USA
[2] Adv Biosci Labs, Kensington, NSW, Australia
[3] FAST Syst Inc, Gaithersburg, MD USA
[4] Univ Washington, Sch Med, Retrovirus Lab, Seattle, WA 98195 USA
[5] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA
[6] Brown Univ, Div Biol & Med, Dept Biochem Mol Biol & Cell Biol, Providence, RI 02912 USA
关键词
antiviral drugs; 9-Nitrocamptothecin; human peripheral blood lymphocytes; HIV/AIDS;
D O I
10.1002/jmv.1042
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The ability of the anti-cancer drug, 9-Nitro-camptothecin (9NC), to inhibit replication of HIV-1 in clinically relevant primary lymphocytic cells was studied. Primary peripheral blood lymphocytes (PBLs) from a non-infected donor were freshly infected with HIV-1 and treated with 9NC by using three different treatment schedules. Cells were monitored for cytotoxicity by the XTT metabolic cell proliferation assay and a sensitive flow cytometric assay that was capable of measuring cell cycle changes and apoptosis. 9NC inhibited replication of HIV-1 in PBLs by greater than 95% in a dose-dependent manner as measured by the level of extracellular HIV-1 p24 release. Similar results were observed, whether 9NC was applied in a single, double, or triple dose regimen. Minimal cytotoxicity was observed for both non-infected and infected PBLs, as determined by the XTT assay. Moreover, 9NC induced apoptosis within 24 hours of drug treatment in freshly infected, but not non-infected, PBLs. The data showed that 9NC reduced replication of HIV-1 in primary human lymphocytes; thus, it indicates the potential clinical utility of this drug as an alternative or adjunct therapy for HIV-infection/AIDS. J. Med. Virol. 64:238-244, 2001. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:238 / 244
页数:7
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