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9‐Nitrocamptothecin inhibits HIV‐1 replication in human peripheral blood lymphocytes: A potential alternative for HIV‐infection/AIDS therapy
Author(s) -
Hung ChiaLing,
Doniger Jay,
Palini Alessio,
Snyder Stuart W.,
Radonovich Michael F.,
Brady John N.,
Pantazis Panayotis,
Sadaie M. Reza
Publication year - 2001
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1042
Subject(s) - flow cytometry , cytotoxicity , apoptosis , biology , virology , cell cycle , viral replication , immunology , oncolytic virus , pharmacology , virus , in vitro , biochemistry
The ability of the anti‐cancer drug, 9‐Nitrocamptothecin (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. © 2001 Wiley‐Liss, Inc.