Abstract
Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.
Highlights
The phosphorylation of eIF4E plays a critical role in controlling protein translation
EIF4E Phosphorylation Is Important for murine norovirus 1 (MNV1) Translation and Replication—Previous studies have demonstrated that the VPg protein of caliciviruses acts as a proteinaceous cap substitute to initiate translation by interacting with eIF4E both in vitro and in vivo [37, 38]
The interaction with eIF4E is required for the translation of feline calicivirus (FCV) RNA in in vitro RRL systems, it plays little to no role in MNV translation in vitro or in murine microglial cells [38, 39]
Summary
The phosphorylation of eIF4E plays a critical role in controlling protein translation. The depletion of eIF4E or the addition of 4E-BP1 has little to no impact on MNV1 VPg-linked RNA translation in rabbit reticulocyte lysates or in cells [38, 39] Based on these studies, we hypothesized that eIF4E could play an important role during the norovirus life cycle through the modulation of eIF4E phosphorylation mediated by the mitogen-activated protein kinase (MAPK) pathway. Using polysomal profile analysis, we show that phosphorylated eIF4E relocates to the polysomes during infection, and we provide evidence that this could induce the translational control of a subset of mRNAs during infection These results suggest that regulation of eIF4E activity plays a role during MNV1 infection to regulate translation of specific host mRNAs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
