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Binding and Relocalization of PKR 1 by Murine Cytomegalovirus

Child, Stephanie J. and Geballe, Adam P. (2009) Binding and Relocalization of PKR 1 by Murine Cytomegalovirus. The Journal of Virology, 83 (4). pp. 1790-1799. ISSN 0022-538X

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Article URL: http://jvi.asm.org/cgi/reprint/83/4/1790

Abstract

Many viruses have evolved mechanisms to evade the repression of translation mediated by protein kinase R (PKR). In the case of murine cytomegalovirus (MCMV), the protein products of two essential genes, m142 and m143, bind to dsRNA and block phosphorylation of PKR and eukaryotic initiation factor 2. A distinctive feature of MCMV is that two proteins are required to block PKR activation whereas other viral dsRNA-binding proteins that prevent PKR activation contain all the necessary functions in a single protein. In order to better understand the mechanism by which MCMV evades the PKR response, we investigated the associations of pm142 and pm143 with each other and with PKR. Both pm142 and pm143 interact with PKR in infected and transfected cells. However, the ~200 kDa pm142:pm143 complex that forms in these cells does not contain substantial amounts of PKR, suggesting that the interactions between pm142:pm143 and PKR are unstable or transient. The stable, soluble pm142:pm143 complex appears to be a heterotetramer consisting of two molecules of pm142 associated with each other and each one binding to and stabilizing a monomer of pm143. MCMV infection also causes relocalization of PKR into the nucleus and to an insoluble cytoplasmic compartment. These results suggest a model in which the pm142:pm143 multimer interacts with PKR and causes its sequestration in cellular compartments where it is unable to shut off translation and repress viral replication.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first four months following publication.
DOI: 10.1128/JVI.01484-08
PubMed ID: 19073740
PMCID: PMC2643750
Grant Numbers: R01 AI026672-19
Keywords or MeSH Headings: * Animals * Cell Line * Cell Nucleus/chemistry * Cytoplasm/chemistry * Humans * Mice * Muromegalovirus/physiology* * Protein Binding * Protein Multimerization * Protein Transport * Viral Proteins/metabolism* * eIF-2 Kinase/antagonists & inhibitors* * eIF-2 Kinase/metabolism*
Subjects: Cellular and Organismal Processes > Genetic processes > Translation
Organisms > Viruses > DNA viruses
Molecules > Proteins
Depositing User: Library Staff
Date Deposited: 03 Dec 2008 19:25
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/85

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