Rubella virus capsid protein interacts with poly(a)-binding protein and inhibits translation.
During virus assembly, the capsid proteins of RNA viruses bind to genomic RNA to form nucleocapsids. However, it is now evident that capsid proteins have additional functions that are unrelated to nucleocapsid formation. Specifically, their interactions with cellular proteins may influence signaling pathways or other events that affect virus replication. Here we report that the rubella virus (RV) capsid protein binds to poly(A)-binding protein (PABP), a host cell protein that enhances translational efficiency by circularizing mRNAs. Infection of cells with RV resulted in marked increases in the levels of PABP, much of which colocalized with capsid in the cytoplasm. Mapping studies revealed that capsid binds to the C-terminal half of PABP, which interestingly is the region that interacts with other translation regulators, including PABP-interacting protein 1 (Paip1) and Paip2. The addition of capsid to in vitro translation reaction mixtures inhibited protein synthesis in a dose-dependent manner; however, the capsid block was alleviated by excess PABP, indicating that inhibition of translation occurs through a stoichiometric mechanism. To our knowledge, this is the first report of a viral protein that inhibits protein translation by sequestration of PABP. We hypothesize that capsid-dependent inhibition of translation may facilitate the switch from viral translation to packaging RNA into nucleocapsids.
Ilkow
Carolina S
CS
Department of Cell Biology, University of Alberta, 5-14 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
Mancinelli
Valeria
V
Beatch
Martin D
MD
Hobman
Tom C
TC
D001665:Binding Sites; D036022:Capsid Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D012412:Rubella virus / Q000737:chemistry / Q000502:physiology*
D036022:Capsid Proteins; D039102:Poly(A)-Binding Proteins