RNA interference directed to CDK2 inhibits HIV-1 transcription

被引:32
作者
Ammosova, T
Berro, R
Kashanchi, F
Nekhai, S
机构
[1] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA
[2] Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC 20059 USA
[3] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA
关键词
HIV-1; CDK2; transcription; RNA interference; Tat;
D O I
10.1016/j.virol.2005.06.041
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In the present study, CDK2-specific RNA interference in cultured HEK293T cells inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells and potently blocked TNF alpha-induced HIV-1 viral replication in OM 10.1 cells. CDK2-specific RNA interference did not have an effect on cell cycle progression, but it augmented TNF alpha-induced apoptosis of OM 10.1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:171 / 178
页数:8
相关论文
共 15 条
[1]   Antiviral activity of CYC202 in HIV-1-infected cells [J].
Agbottah, E ;
de la Fuente, C ;
Nekhai, S ;
Barnett, A ;
Gianella-Borradori, A ;
Pumfery, A ;
Kashanchi, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (04) :3029-3042
[2]   Nuclear protein phosphatase-1 regulates HIV-1 transcription [J].
Ammosova, T ;
Jerebtsova, M ;
Beullens, M ;
Voloshin, Y ;
Ray, PE ;
Kumar, A ;
Bollen, M ;
Nekhai, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) :32189-32194
[3]   Cdk2 knockout mice are viable [J].
Berthet, C ;
Aleem, E ;
Coppola, V ;
Tessarollo, L ;
Kaldis, P .
CURRENT BIOLOGY, 2003, 13 (20) :1775-1785
[4]   Loss of G1/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1 [J].
Clark, E ;
Santiago, F ;
Deng, LW ;
Chong, SY ;
de la Fuente, C ;
Wang, L ;
Fu, P ;
Stein, D ;
Denny, T ;
Lanka, V ;
Mozafari, F ;
Okamoto, T ;
Kashanchi, F .
JOURNAL OF VIROLOGY, 2000, 74 (11) :5040-5052
[5]   HIV-1 tat interaction with RNA polymerase IIC-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter [J].
Deng, LW ;
Ammosova, T ;
Pumfery, A ;
Kashanchi, F ;
Nekhai, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (37) :33922-33929
[6]   Cell cycle-regulated transcription by the human immunodeficiency virus type 1 Tat transactivator [J].
Kashanchi, F ;
Agbottah, ET ;
Pise-Masison, CA ;
Mahieux, R ;
Duvall, J ;
Kumar, A ;
Brady, JN .
JOURNAL OF VIROLOGY, 2000, 74 (02) :652-660
[7]   DETECTION OF REPLICATION-COMPETENT AND PSEUDOTYPED HUMAN-IMMUNODEFICIENCY-VIRUS WITH A SENSITIVE CELL-LINE ON THE BASIS OF ACTIVATION OF AN INTEGRATED BETA-GALACTOSIDASE GENE [J].
KIMPTON, J ;
EMERMAN, M .
JOURNAL OF VIROLOGY, 1992, 66 (04) :2232-2239
[8]  
Malumbres M, 2003, ADV EXP MED BIOL, V532, P1
[9]   A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity [J].
Nekhai, S ;
Shukla, RR ;
Kumar, A .
JOURNAL OF VIROLOGY, 1997, 71 (10) :7436-7441
[10]   Cell cycle-dependent stimulation of the HIV-1 promoter by Tat-associated CAK activator [J].
Nekhai, S ;
Shukla, RR ;
Fernandez, A ;
Kumar, A ;
Lamb, NJC .
VIROLOGY, 2000, 266 (02) :246-256