Kyratsous Christos A, Silverstein Saul J
Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032, USA.
J Virol. 2007 Jul;81(14):7491-503. doi: 10.1128/JVI.00442-07. Epub 2007 May 2.
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.
水痘带状疱疹病毒（VZV）在宿主的背根神经节中建立终身潜伏感染。在潜伏期间，可检测到一部分病毒编码的调节蛋白；然而，它们被排除在细胞核之外。ORF29p是一种单链DNA结合蛋白，是这些潜伏相关蛋白之一。我们寻找与ORF29p相互作用的细胞蛋白，并鉴定出BAG3。在VZV的裂解复制过程中，BAG3、Hsp70/Hsc70和Hsp90与ORF29p在核转录/复制工厂中共定位。用安莎霉素类抗生素对Hsp90活性进行药理干预或用小干扰RNA耗尽BAG3会导致病毒复制受到抑制。通过用外源性BAG3互补，可恢复BAG3缺失细胞系中的复制。宿主伴侣蛋白活性的改变提供了一种调节病毒复制的新方法。
