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Journal of Virology, October 2006, p. 10173-10180, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00905-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Double-Stranded RNA Binding by a Heterodimeric Complex of Murine Cytomegalovirus m142 and m143 Proteins

Stephanie J. Child,1 Laura K. Hanson,2 Crystal E. Brown,1,{dagger} Deanna M. Janzen,1,{ddagger} and Adam P. Geballe1*

Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and Departments of Microbiology and Medicine, University of Washington, Seattle, Washington 98115,1 Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 235012

Received 3 May 2006/ Accepted 12 July 2006

In response to viral infection, cells activate a variety of antiviral responses, including several that are triggered by double-stranded (ds) RNA. Among these are the protein kinase R and oligoadenylate synthetase/RNase L pathways, both of which result in the shutoff of protein synthesis. Many viruses, including human cytomegalovirus, encode dsRNA-binding proteins that prevent the activation of these pathways and thereby enable continued protein synthesis and viral replication. We have extended these analyses to another member of the ß subfamily of herpesviruses, murine cytomegalovirus (MCMV), and now report that products of the m142 and m143 genes together bind dsRNA. Coimmunoprecipitation experiments demonstrate that these two proteins interact in infected cells, consistent with their previously reported colocalization. Jointly, but not individually, the proteins rescue replication of a vaccinia virus mutant with a deletion of the dsRNA-binding protein gene E3L (VV{Delta}E3L). Like the human cytomegalovirus dsRNA-binding protein genes TRS1 and IRS1, m142 and m143 are members of the US22 gene family. We also found that two other members of the MCMV US22 family, M23 and M24, encode dsRNA-binding proteins, but they do not rescue VV{Delta}E3L replication. These results reveal that MCMV, like many other viruses, encodes dsRNA-binding proteins, at least two of which can inhibit dsRNA-activated antiviral pathways. However, unlike other well-studied examples, the MCMV proteins appear to act in a heterodimeric complex.

* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, MS C2-023, Seattle, WA 98109-1024. Phone: (206) 667-5122. Fax: (206) 667-6523. E-mail: ageballe{at}fhcrc.org.

{dagger} Present address: Case Western Reserve School of Medicine, Cleveland, OH 44106.

{ddagger} Present address: Department of Molecular and Cell Biology, 91 North Eagleville Rd., U-3125, University of Connecticut, Storrs, CT 06269.

Journal of Virology, October 2006, p. 10173-10180, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.00905-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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