BAG3, a host cochaperone, facilitates varicella-zoster virus replication.
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.
Kyratsous
Christos A
CA
Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 W. 168th St., New York, NY 10032, USA.
Silverstein
Saul J
SJ
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D016227:Benzoquinones / Q000494:pharmacology; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D016366:Open Reading Frames; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D014779:Virus Replication / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D016227:Benzoquinones; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D046988:Proteasome Endopeptidase Complex; C001277:geldanamycin