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Cell Host Microbe. 2012 Jul 19;12(1):71-85. doi: 10.1016/j.chom.2012.05.013.

Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection.

Author information

1
Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Germany.

Abstract

Virus infection-induced global protein synthesis suppression is linked to assembly of stress granules (SGs), cytosolic aggregates of stalled translation preinitiation complexes. To study long-term stress responses, we developed an imaging approach for extended observation and analysis of SG dynamics during persistent hepatitis C virus (HCV) infection. In combination with type 1 interferon, HCV infection induces highly dynamic assembly/disassembly of cytoplasmic SGs, concomitant with phases of active and stalled translation, delayed cell division, and prolonged cell survival. Double-stranded RNA (dsRNA), independent of viral replication, is sufficient to trigger these oscillations. Translation initiation factor eIF2α phosphorylation by protein kinase R mediates SG formation and translation arrest. This is antagonized by the upregulation of GADD34, the regulatory subunit of protein phosphatase 1 dephosphorylating eIF2α. Stress response oscillation is a general mechanism to prevent long-lasting translation repression and a conserved host cell reaction to multiple RNA viruses, which HCV may exploit to establish persistence.

PMID:
22817989
PMCID:
PMC3873964
DOI:
10.1016/j.chom.2012.05.013
[Indexed for MEDLINE]
Free PMC Article

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