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Journal of Virology, July 2007, p. 7491-7503, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00442-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

BAG3, a Host Cochaperone, Facilitates Varicella-Zoster Virus Replication{triangledown}

Christos A. Kyratsous and Saul J. Silverstein*

Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, New York 10032

Received 1 March 2007/ Accepted 25 April 2007

Varicella-zoster virus (VZV) establishes a lifelong latent infection in the dorsal root ganglia of the host. During latency, a subset of virus-encoded regulatory proteins is detected; however, they are excluded from the nucleus. ORF29p, a single-stranded DNA binding protein, is one of these latency-associated proteins. We searched for cell proteins that interact with ORF29p and identified BAG3. BAG3, Hsp70/Hsc70, and Hsp90 colocalize with ORF29p in nuclear transcription/replication factories during lytic replication of VZV. Pharmacological intercession of Hsp90 activity with ansamycin antibiotics or depletion of BAG3 by small interfering RNA results in inhibition of virus replication. Replication in BAG3-depleted cell lines is restored by complementation with exogenous BAG3. Alteration of host chaperone activity provides a novel means of regulating virus replication.


* Corresponding author. Mailing address: Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-8149. Fax: (212) 305-5106. E-mail: sjs6{at}columbia.edu

{triangledown} Published ahead of print on 2 May 2007.


Journal of Virology, July 2007, p. 7491-7503, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00442-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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