Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation

English version

Autoři: Michèle Brocard ^aff001; Valentina Iadevaia ^aff001; Philipp Klein ^aff002; Belinda Hall ^aff001; Glenys Lewis ^aff001; Jia Lu ^aff003; James Burke ^aff004; Margaret M. Willcocks ^aff001; Roy Parker ^aff004; Ian G. Goodfellow ^aff003; Alessia Ruggieri ^aff002; Nicolas Locker ^aff001
Působiště autorů: Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom ^aff001; Department of Infectious Diseases, Molecular Virology, Centre for Integrative Infectious Disease Research, University of Heidelberg, Heidelberg, Germany ^aff002; Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom ^aff003; Department of Biochemistry, University of Colorado, Boulder, CO, United States of America ^aff004; Howard Hughes Medical Institute, University of Colorado, Boulder, CO, United States of America ^aff005
Vyšlo v časopise: Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation. PLoS Pathog 16(1): e1008250. doi:10.1371/journal.ppat.1008250
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1008250

Souhrn

Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Here we examined how norovirus interacts with the eIF2α signaling axis controlling translation and stress granules. While norovirus infection represses host cell translation, our mechanistic analyses revealed that eIF2α signaling mediated by the stress kinase GCN2 is uncoupled from translational stalling. Moreover, infection results in a redistribution of the RNA-binding protein G3BP1 to replication complexes and remodelling of its interacting partners, allowing the avoidance from canonical stress granules. These results define novel strategies by which norovirus undergo efficient replication whilst avoiding the host stress response and manipulating the G3BP1 interactome.

Klíčová slova:

Viral replication – Protein translation – Immunoprecipitation – Cellular stress responses – Phosphorylation – Norovirus – Interaction networks – Calicivirus infection

Zdroje

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