Norovirus infection results in assembly of virus-specific G3BP1 granules and evasion of eIF2α signaling
| Autor: | Belinda S. Hall, Alessia Ruggieri, Ian Goodfellow, Valentina Iadevaia, Glenys Lewis, James M. Burke, Michèle Brocard, Roy Parker, Jia Lu, Philipp Klein, Nicolas Locker |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
ved/biology viruses ved/biology.organism_classification_rank.species Defence mechanisms Biology medicine.disease_cause Virus 3. Good health Cell biology Fight-or-flight response 03 medical and health sciences 0302 clinical medicine Stress granule Eukaryotic initiation factor Norovirus medicine Protein biosynthesis 030217 neurology & neurosurgery 030304 developmental biology Murine norovirus |
| DOI: | 10.1101/490318 |
| Popis: | During viral infection, the accumulation of RNA replication intermediates or viral proteins imposes major stress on the host cell. In response, cellular stress pathways can rapidly impose defence mechanisms by shutting off the protein synthesis machinery, which viruses depend on, 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. Previously we showed that murine norovirus (MNV) regulates the activity of eukaryotic initiation factors (eIFs). Here we examined how MNV interacts with the eIF2α signaling axis controlling translation and stress granules accumulation. We show that while MNV infection represses host cell translation, it results in the assembly of virus-specific granules rather than stress granules. Further mechanistic analyses revealed that eIF2α signaling is uncoupled from translational stalling. Moreover the interaction of the RNA-binding protein G3BP1 with viral factors together with a redistribution of its cellular interacting partners could explain norovirus evasion of stress granules assembly. These results identify novel strategies by which norovirus ensure efficient replication propagation by manipulating the host stress response. |
| Databáze: | OpenAIRE |
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