Analysis of Connections Between Host Cytoplasmic Processing Bodies and Viral Life Cycles

Abstract

In the past few years, cytoplasmic processing bodies (P-Bodies) have been identified in eukaryotic cells. P-bodies have roles in translational repression, mRNA storage, mRNA decay and are conserved cytoplasmic aggregations of non-translating mRNAs in conjunction with translation repression and mRNA degradation factors. In this work, I, in collaboration with others provide evidence for a new biological role for P-bodies in viral life cycles. This work can be summarized thus:In a collaborative effort, I have identified connections between retrovirallike transposon life cycles and P-bodies. For example, genetic evidence in yeast indicates that key proteins within P-bodies are required for the life cycles of the Ty1 and Ty3 retrotransposons. Moreover, Ty3 genomic RNA (gRNA) as well as viral structural proteins accumulate in P-bodies, suggesting that P-bodies may serve as sites of viral assembly.Second, I have shown, with assistance of collaborators, that the positivestrand RNA virus, Brome Mosaic Virus (BMV) gRNA accumulates in P-bodies Moreover, viral RNA dependent RNA polymerase (RdRp) colocalizes with and co-immunoprecipitates with the P-body protein Lsm1p, suggesting that P-bodies may participate in viral replication. Remarkably, the accumulation BMV gRNA in P-bodies is dependent on cis-elements that have been demonstrated to play critical roles in viral RNA replication.The identification of P-bodies as sites of accumulation of viral gRNA and viral proteins of both retro-virus like elements and positive-stranded RNA viruses, expands the list of important biological roles played by P-bodies. Since P-body proteins and structure are highly conserved, these findings imply that Pbodies will be important for other RNA viruses.