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

98 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

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Virus Diseases
Hepacivirus
Cytoplasmic Granules
Protein Phosphatase 1
Peptide Initiation Factors
Interferon Type I
Double-Stranded RNA
RNA Viruses
Cell Division
Protein Kinases
Cell Survival
Up-Regulation
Phosphorylation
Observation
Proteins

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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
Ruggieri, Alessia ; Dazert, Eva ; Metz, Philippe ; Hofmann, Sarah ; Bergeest, Jan-Philip ; Mazur, Johanna ; Bankhead, Peter ; Hiet, Marie-Sophie ; Kallis, Stephanie ; Alvisi, Gualtiero ; Samuel, Charles ; Lohmann, Volker ; Kaderali, Lars ; Rohr, Karl ; Frese, Michael ; Stoecklin, Georg ; Bartenschlager, Ralf. / Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. In: Cell Host Microbe. 2012 ; Vol. 12, No. 1. pp. 71-85.
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Ruggieri, A, Dazert, E, Metz, P, Hofmann, S, Bergeest, J-P, Mazur, J, Bankhead, P, Hiet, M-S, Kallis, S, Alvisi, G, Samuel, C, Lohmann, V, Kaderali, L, Rohr, K, Frese, M, Stoecklin, G & Bartenschlager, R 2012, 'Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection', Cell Host Microbe, vol. 12, no. 1, pp. 71-85. https://doi.org/10.1016/J.CHOM.2012.05.013

Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. / Ruggieri, Alessia; Dazert, Eva; Metz, Philippe; Hofmann, Sarah; Bergeest, Jan-Philip; Mazur, Johanna; Bankhead, Peter; Hiet, Marie-Sophie; Kallis, Stephanie; Alvisi, Gualtiero; Samuel, Charles; Lohmann, Volker; Kaderali, Lars; Rohr, Karl; Frese, Michael; Stoecklin, Georg; Bartenschlager, Ralf.

In: Cell Host Microbe, Vol. 12, No. 1, 2012, p. 71-85.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection

AU - Ruggieri, Alessia

AU - Dazert, Eva

AU - Metz, Philippe

AU - Hofmann, Sarah

AU - Bergeest, Jan-Philip

AU - Mazur, Johanna

AU - Bankhead, Peter

AU - Hiet, Marie-Sophie

AU - Kallis, Stephanie

AU - Alvisi, Gualtiero

AU - Samuel, Charles

AU - Lohmann, Volker

AU - Kaderali, Lars

AU - Rohr, Karl

AU - Frese, Michael

AU - Stoecklin, Georg

AU - Bartenschlager, Ralf

PY - 2012

Y1 - 2012

N2 - 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

AB - 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

KW - Hepatitis C virus

KW - Protein translation

KW - Interferon

U2 - 10.1016/J.CHOM.2012.05.013

DO - 10.1016/J.CHOM.2012.05.013

M3 - Article

VL - 12

SP - 71

EP - 85

JO - Cell Host Microbe

JF - Cell Host Microbe

SN - 1931-3128

IS - 1

ER -