Phosphorylation and membrane association of the Rubella virus capsid protein is important for its anti-apoptotic function.
Rubella virus (RV), a member of Togaviridae, is an important human pathogen that can cause severe defects in the developing fetus. Compared to other togaviruses, RV replicates very slowly suggesting that it must employ effective mechanisms to delay the innate immune response. A recent study by our laboratory revealed that the capsid protein of RV is a potent inhibitor of apoptosis. A primary mechanism by which RV capsid interferes with programmed cell death appears to be through interaction with the pro-apoptotic Bcl-2 family member Bax. In the present study, we report that the capsid protein also blocks IRF3-dependent apoptosis induced by the double-strand RNA mimic polyinosinic-polycytidylic acid. In addition, analyses of cis-acting elements revealed that phosphorylation and membrane association are important for its anti-apoptotic function. Finally, the observation that hypo-phosphorylated capsid binds Bax just as well as wild-type capsid protein suggests that interaction with this pro-apoptotic host protein in and of itself is not sufficient to block programmed cell death. This provides additional evidence that this viral protein inhibits apoptosis through multiple mechanisms.
Department of Cell Biology, University of Alberta, 5-14 Medical Sciences Building, Edmonton, Canada, T6G 2H7.
Steven
S
Willows
Carolina S
CS
Ilkow
Tom C
TC
Hobman
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D045304:Cytochromes c / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012412:Rubella virus / Q000378:metabolism*; D014709:Vero Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D036022:Capsid Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011070:Poly I-C