The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members

Autor: C. Michael Knudson, Paul D Ogg, Peter J McDonell, Brent J. Ryckman, Richard J. Roller
Rok vydání: 2004
Předmět:
Zdroj: Virology. 319:212-224
ISSN: 0042-6822
DOI: 10.1016/j.virol.2003.10.019
Popis: The Us3 protein kinase encoded by herpes simplex virus type-1 (HSV-1) suppresses apoptosis in infected cells and is sufficient to block apoptosis induced by overexpression of Bad [Proc. Natl. Acad. Sci. 98 (2001) 10410]. While Us3 can induce phosphorylation of Bad, phosphorylation of Bad is dispensable for Us3 anti-apoptotic function [J. Virol. 77 (2003) 6567]. We extend the findings with Bad to demonstrate that Us3 blocks apoptosis induced by overexpression of Bid, a factor parallel to Bad in the apoptotic pathway, and Bax, a factor downstream of Bad in the apoptotic pathway. A previous report suggested that Us3 exerts its effects at a premitochondrial stage [J. Virol. 75 (2001) 5491], but our results suggest that Us3 exerts anti-apoptotic effects downstream of the mitochondria. We show that the kinase activity of Us3 is necessary for Us3 anti-apoptotic effects, because a catalytically inactive form of Us3 was unable to block apoptosis. A second function of Us3, primary envelopment during viral egress, is conserved in the Us3 homologue of Pseudorabies virus (PRV) [J. Gen. Virol. 82 (2001) 2363]. Experiments published here demonstrate that PRV Us3 can also block apoptosis induced by Bax, suggesting that the anti-apoptotic activity of Us3 is conserved across α-herpesviruses.
Databáze: OpenAIRE
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