HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation

被引：14

作者：

Okamoto, H

Cujec, TP

Peterlin, BM

Okamoto, T

机构：

[1] Nagoya City Univ, Sch Med, Dept Mol Genet, Mizuho Ku, Nagoya, Aichi 4678601, Japan

[2] Univ Calif San Francisco, Dept Med Microbiol & Immunol, Howard Hughes Med Inst, San Francisco, CA 94115 USA

来源：

VIROLOGY | 2000年 / 270卷 / 02期

关键词：

D O I：

10.1006/viro.2000.0311

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The activation of the HIV-1 long terminal repeat (LTR) by the viral transcriptional transactivator Tat is an essential step in the viral replication cycle. To increase the processivity of RNA polymerase II, Tat interacts with the positive transcription elongation factor b (P-TEFb) and cyclin-dependent kinase (CDK)-activating kinase (CAK). in this study, we demonstrate that a pseudo-substrate peptide for CDK7, mC2p, inhibits HIV-1 replication as well as Tat transactivation. Specifically, mC2p blocks only the activity of CAK and not that of P-TEFb. Moreover, mC2p inhibits Tat transactivation and HIV replication. Therefore, the activation of CDK7 by Tat is considered a critical step of Tat transactivation and mC2p and related compounds represent potential candidates for novel anti-HIV therapeutics. (C) 2000 Academic Press.

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收藏

页码：337 / 344

页数：8

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