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

Paul D Ogg; Peter J McDonell; Brent J Ryckman; C.Michael Knudson; Richard J Roller

doi:10.1016/j.virol.2003.10.019

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

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

Paul D Ogg, Peter J McDonell, Brent J Ryckman, C.Michael Knudson and Richard J Roller

Virology (New York, N.Y.), Vol.319(2), pp.212-224

2004

DOI: 10.1016/j.virol.2003.10.019

PMID: 14980482

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Abstract

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.

Mitochondria

Us3

Kinase

Herpes simplex virus type-1, HSV-1

Programmed cell death

Pseudorabies virus, PRV

Protein

Apoptosis

Details

Title: Subtitle: The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members
Creators: Paul D Ogg - Molecular Biology Program, Roy J. and Lucille P. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
Peter J McDonell - Microbiology Department, Roy J. and Lucille P. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
Brent J Ryckman - Microbiology Department, Roy J. and Lucille P. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
C.Michael Knudson - Molecular Biology Program, Roy J. and Lucille P. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
Richard J Roller - Molecular Biology Program, Roy J. and Lucille P. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.319(2), pp.212-224
DOI: 10.1016/j.virol.2003.10.019
PMID: 14980482
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Language: English
Date published: 2004
Academic Unit: Microbiology and Immunology; Pathology; Radiation Oncology
Record Identifier: 9984001203602771

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