Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation
- University of Cambridge, United Kingdom
- Washington University School of Medicine, United States
- Karolinska Institutet, Sweden
- University of Surrey, United Kingdom
- Yale School of Medicine, United States
Abstract
Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating ribosome recruitment. Our data uncovers a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifies the first host factor with pan-norovirus pro-viral activity.
Data availability
VPg proteomics raw data, search results and FASTA files can be found as part of PRIDE submission PXD007585. Flag-virus proteomics raw data, search results and FASTA files can be found as part of PRIDE submission PXD011779.
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VPg proteomics raw dataPRIDE PRoteomics IDEntifications, PXD007585.
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Flag-virus proteomics raw dataPRIDE PRoteomics IDEntifications, PXD011779.
Article and author information
Author details
Marc Dominik Panas
Funding
Wellcome (207498/Z/17/Z)
- Myra Hosmillo
- Jia Lu
- James B Eaglesham
- Xinjie Wang
- Edward Emmott
- Patricia Domingues
- Yasmin Chaudhry
- Tim J Fitzmaurice
- Matthew KH Tung
- Ian G Goodfellow
National Institutes of Health (AI128043)
- Craig B Wilen
Biotechnology and Biological Sciences Research Council (BB/N001176/1)
- Jia Lu
- Ian G Goodfellow
Wellcome (104914/Z/14/Z)
- Ian G Goodfellow
Burroughs Wellcome Fund
- Craig B Wilen
Churchill College, University of Cambridge
- James B Eaglesham
Biotechnology and Biological Sciences Research Council (BB/000943N/1)
- Nicolas Locker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Hosmillo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation
eLife 8:e46681.
https://doi.org/10.7554/eLife.46681
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