期刊
CELL HOST & MICROBE
卷 12, 期 1, 页码 71-85出版社
CELL PRESS
DOI: 10.1016/j.chom.2012.05.013
关键词
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资金
- Deutsche Forschungsgemeinschaft [FOR1202 TP1, TP3, SFB/TRR77, TPA1]
- Bundesministerium fur Bildung und Forschung [01 KI 0786]
- European Union
- Cell-Networks Cluster of Excellence
- U.S. National Institutes of Health [AI-12520, -20611]
- Viroquant project
- Viroquant HBIGS-Stipendium
- DKFZ-ZMBH Alliance
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 elF2 alpha 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 elF2 alpha. 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.
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