Abstract
In this review, we provide an overview of the strategies developed by caliciviruses to subvert or regulate the host protein synthesis machinery to their advantage. As intracellular obligate parasites, viruses strictly depend on the host cell resources to produce viral proteins. Thus, many viruses have developed strategies that regulate the function of the host protein synthesis machinery, often leading to preferential translation of viral mRNAs. Caliciviruses lack a 5′ cap structure but instead have a virus-encoded VPg protein covalently linked to the 5′ end of their mRNAs. Furthermore, they encode 2–4 open reading frames within their genomic and subgenomic RNAs. Therefore, they use alternative mechanisms for translation whereby VPg interacts with eukaryotic initiation factors (eIFs) to act as a proteinaceous cap-substitute, and some structural proteins are produced by reinitiation of translation events. This review discusses our understanding of these key mechanisms during caliciviruses infection as well as recent insights into the global regulation of eIF4E activity.
Highlights
In this review, we provide an overview of the strategies developed by caliciviruses to subvert or regulate the host protein synthesis machinery to their advantage
They use alternative mechanisms for translation whereby VPg interacts with eukaryotic initiation factors to act as a proteinaceous cap-substitute, and some structural proteins are produced by reinitiation of translation events
Our current knowledge is derived from other caliciviruses used as representative models, including feline calicivirus (FCV), murine norovirus (MNV), and porcine sapovirus (PSaV), due to both the development of reverse genetics systems and the availability of cell cultures for their propagation
Summary
The Caliciviridae family comprises small RNA viruses of both medical and veterinary importance. Using cap-sepharose pull-down and eIF4E-depletion with siRNA or 4EBP1 proteins, it was shown that the interaction of VPg with eIF4E is conserved among the Caliciviridae [40,43,45] While this interaction is essential for initiation of translation in FCV [40], RHDV [46], and PSaV [45], MNV translation is not affected by the depletion of eIF4E nor by separation of the eIF4E-binding domain from eIF4G [43,44]. In addition to interactions with members of the eIF4F complex, Daughenbaugh et al [38] were able to demonstrate direct binding of eIF3 to the VPg from the prototype human norovirus Norwalk (NV) Both the genomic and the subgenomic 51 ends of FCV RNA can interact with the translation factor PTB [53]. Helix 26 of the 18S rRNA (as depicted by dotted lines), which help docking the ribosome onto the viral mRNA, allowing reinitiation on the down-stream ORF
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