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

Alessia Ruggieri, Eva Dazert, Philippe Metz, Sarah Hofmann, Jan-Philip Bergeest, Johanna Mazur, Peter Bankhead, Marie-Sophie Hiet, Stephanie Kallis, Gualtiero Alvisi, Charles Samuel, Volker Lohmann, Lars Kaderali, Karl Rohr, Michael Frese, Georg Stoecklin, Ralf Bartenschlager

Research output: Contribution to journalArticle

104 Citations (Scopus)

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 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
Original languageEnglish
Pages (from-to)71-85
Number of pages15
JournalCell Host Microbe
Volume12
Issue number1
DOIs
Publication statusPublished - 2012

    Fingerprint

Cite this

Ruggieri, A., Dazert, E., Metz, P., Hofmann, S., Bergeest, J-P., Mazur, J., ... Bartenschlager, R. (2012). Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe, 12(1), 71-85. https://doi.org/10.1016/J.CHOM.2012.05.013