Novel strategy for anti-HIV-1 action: selective cytotoxic effect of N-myristoyltransferase inhibitor on HIV-1-infected cells

FEBS Lett. 2002 Sep 11;527(1-3):138-42. doi: 10.1016/s0014-5793(02)03199-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / antagonists & inhibitors*
  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Adenocarcinoma / virology
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cells, Cultured
  • Colonic Neoplasms / virology
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • HIV-1 / enzymology
  • HIV-1 / pathogenicity*
  • Humans
  • RNA, Messenger / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / virology

Substances

  • Anti-HIV Agents
  • Enzyme Inhibitors
  • RNA, Messenger
  • Acyltransferases
  • glycylpeptide N-tetradecanoyltransferase