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Journal of Virology, September 2004, p. 9697-9704, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9697-9704.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Heat Shock Protein 70 Protects Cells from Cell Cycle Arrest and Apoptosis Induced by Human Immunodeficiency Virus Type 1 Viral Protein R

Sergey Iordanskiy,1,2 Yuqi Zhao,3 Larisa Dubrovsky,1 Tatiana Iordanskaya,1 Mongzhong Chen,3 Dong Liang,3 and Michael Bukrinsky1*

The George Washington University, Washington, D.C.,1 Northwestern University Feinberg School of Medicine, Chicago, Illinois,3 The D. I. Ivanovsky Institute of Virology, Moscow, Russia2

Received 3 April 2004/ Accepted 9 June 2004

Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is an accessory protein that plays an important role in viral pathogenesis. This pathogenic activity of Vpr is related in part to its capacity to induce cell cycle G2 arrest and apoptosis of target T cells. A screening for multicopy suppressors of these Vpr activities in fission yeast identified heat shock protein 70 (Hsp70) as a suppressor of Vpr-induced cell cycle arrest. Hsp70 is a member of a family of molecular chaperones involved in innate immunity and protection from environmental stress. In this report, we demonstrate that HIV-1 infection induces Hsp70 in target cells. Overexpression of Hsp70 reduced the Vpr-dependent G2 arrest and apoptosis and also reduced replication of the Vpr-positive, but not Vpr-deficient, HIV-1. Suppression of Hsp70 expression by RNA interference (RNAi) resulted in increased apoptosis of cells infected with a Vpr-positive, but not Vpr-defective, HIV-1. Replication of the Vpr-positive HIV-1 was also increased when Hsp70 expression was diminished. Vpr and Hsp70 coimmunoprecipitated from HIV-infected cells. Together, these results identify Hsp70 as a novel anti-HIV innate immunity factor that targets HIV-1 Vpr.


* Corresponding author. Mailing address: Department of Microbiology and Tropical Medicine, The George Washington University, Ross Hall Rm. 734, 2300 Eye St. N.W., Washington, DC 20037. Phone: (202) 994-2036. Fax: (202) 994-2913. E-mail: mtmmib{at}gwumc.edu.


Journal of Virology, September 2004, p. 9697-9704, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9697-9704.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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