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Elife. 2019 Aug 12;8. pii: e46681. doi: 10.7554/eLife.46681.

Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation.

Author information

1
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States.
3
Department of Microbiology, Harvard Medical School, Boston, United States.
4
Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
5
Department of Bioengineering, Northeastern University, Boston, United States.
6
Barnett Institute for Chemical and Biological Analyses, Northeastern University, Boston, United States.
7
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
8
School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom.
9
Department of Laboratory Medicine, Yale School of Medicine, New Haven, United States.
#
Contributed equally

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.

KEYWORDS:

CRISPR; G3BP1; Norovirus; infectious disease; microbiology; stress granule; translation; virus

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