Novel strategy for anti-HIV-1 action: selective cytotoxic effect of N-myristoyltransferase inhibitor on HIV-1-infected cells.
N-myristoyltransferase (NMT) is essential for the survival of eukaryotes and the production of infectious human immunodeficiency virus type-1(HIV-1) by the host cell. In this study, we found decreases in the mRNA levels of human NMT isoforms and the NMT activities in the course of HIV-1 infection in the human T-cell line, CEM. Investigating the cytotoxic effect of the novel synthetic NMT inhibitors on the chronic HIV-1 infected T-cell line, CEM/LAV-1, and the uninfected CEM, revealed that the cytotoxic effect was significantly selective for CEM/LAV-1. This was thought to be due to the difference between the NMT levels of the cell lines. In this paper, we propose that NMT may be a candidate target for anti-HIV-1-infected-cell agents.
Takamune
Nobutoki
N
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, 862-0973, Kumamoto, Japan.
Hamada
Hirotoshi
H
Misumi
Shogo
S
Shoji
Shozo
S
D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000821:virology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000821:virology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015497:HIV-1 / Q000201:enzymology / Q000472:pathogenicity*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase