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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caliciviridae Infections
  • Cell Line
  • DNA Helicases / metabolism*
  • Host-Pathogen Interactions*
  • Humans
  • Mice
  • Norovirus / growth & development*
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Protein Biosynthesis*
  • RNA Helicases / metabolism*
  • RNA Recognition Motif Proteins / metabolism*
  • Viral Proteins / biosynthesis*

Substances

  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • Viral Proteins
  • DNA Helicases
  • G3BP1 protein, human
  • G3bp1 protein, mouse
  • RNA Helicases