Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins.
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 beta 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 (VVDeltaE3L). 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 VVDeltaE3L 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.
Child
Stephanie J
SJ
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, MS C2-023, Seattle, WA 98109-1024, USA.
Hanson
Laura K
LK
Brown
Crystal E
CE
Janzen
Deanna M
DM
Geballe
Adam P
AP
D019281:Dimerization; D017353:Gene Deletion; D047468:Immunoprecipitation; D018146:Muromegalovirus; D011485:Protein Binding; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics / Q000254:growth & development; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C081374:E3L protein, Vaccinia virus; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins