Inhibition of active HIV-1 replication by NF-kappaB inhibitor DHMEQ.
Previous reports indicate that nuclear factor (NF)-kappaB regulates induction of human immunodeficiency virus type 1 (HIV-1) gene expression in latently infected cells. However, the role of NF-kappaB in cells with active HIV-1 replication is not well understood. In this study, we examined the effect of a new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on HIV-1 replication in a human T cell line and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-PBMCs). We further explored the mechanism of DHMEQ-mediated inhibition of HIV-1 replication. DHMEQ inhibited HIV-1 replication in HIV-1-infected Molt-4 and PHA-PBMCs. DHMEQ inhibited constitutive NF-kappaB activity in HIV-1-infected PHA-PBMCs and HIV long terminal repeat promoter activity driven by tumor necrosis factor (TNF)-alpha and the trans-activator Tat. The single-round assay using vesicular stomatitis virus-pseudotyped virus in the human T cell line M8166 indicated that DHMEQ treatment resulted in decreased integration of HIV-1 provirus into the host genome and decreased HIV-1 expression. These results indicate that NF-kappaB regulates early events as well as the initial and accelerated expression of HIV-1 in its life cycle. Therefore, we conclude that NF-kappaB is a molecular target for controlling active HIV-1 replication.
Miyake
Ariko
A
Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Ishida
Takaomi
T
Yamagishi
Makoto
M
Hara
Takuma
T
Umezawa
Kazuo
K
Watanabe
Toshiki
T
Horie
Ryouichi
R
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014779:Virus Replication
D019380:Anti-HIV Agents; D001549:Benzamides; D003512:Cyclohexanones; D007155:Immunologic Factors; D016328:NF-kappa B; C464444:dehydroxymethylepoxyquinomicin