Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells

Chiara Aloise; Jelle G Schipper; Raoul J de Groot; Frank Jm van Kuppeveld

doi:10.1016/j.coi.2022.102254

Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells

Chiara Aloise, Jelle G Schipper, Raoul J de Groot, Frank Jm van Kuppeveld^*

^*Corresponding author for this work

Virology

Research output: Contribution to journal › Review article › peer-review

Abstract

Viruses, when entering their host cells, are met by a fierce intracellular immune defense. One prominent antiviral pathway is the integrated stress response (ISR). Upon activation of the ISR - typically though not exclusively upon detection of dsRNA - translation-initiation factor eukaryotic initiation factor 2 (eIF2) becomes phosphorylated to act as an inhibitor of guanine nucleotide-exchange factor eIF2B. Thus, with the production of ternary complex blocked, a global translational arrest ensues. Successful virus replication hinges on effective countermeasures. Here, we review ISR antagonists and antagonistic mechanisms employed by picorna- and coronaviruses. Special attention will be given to a recently discovered class of viral antagonists that inhibit the ISR by targeting eIF2B, thereby allowing unabated translation initiation even at exceedingly high levels of phosphorylated eIF2.

Original language	English
Article number	102254
Pages (from-to)	1-10
Number of pages	10
Journal	Current Opinion in Immunology
Volume	79
Early online date	28 Sept 2022
DOIs	https://doi.org/10.1016/j.coi.2022.102254
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
This work was supported by Marie Sklodowska-Curie Actions (MSCA) Innovative Training Networks (ITN): H2020-MCSA-ITN-2019 (Grant No 813343 ) and OCENW.KLEIN.344 grant from the Dutch Research Council (to FJMvK).

Publisher Copyright:
© 2022 The Authors

Keywords

Apoptosis
Degradation
Inhibition
Leader protein
Messenger-rna
Mouth-disease virus
Nucleotide exchange
Phosphorylation
Protein-kinase
Translation

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10.1016/j.coi.2022.102254Licence: CC BY

1-s2.0-S0952791522001017-mainFinal published version, 2.76 MBLicence: CC BY

Cite this

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title = "Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells",

abstract = "Viruses, when entering their host cells, are met by a fierce intracellular immune defense. One prominent antiviral pathway is the integrated stress response (ISR). Upon activation of the ISR - typically though not exclusively upon detection of dsRNA - translation-initiation factor eukaryotic initiation factor 2 (eIF2) becomes phosphorylated to act as an inhibitor of guanine nucleotide-exchange factor eIF2B. Thus, with the production of ternary complex blocked, a global translational arrest ensues. Successful virus replication hinges on effective countermeasures. Here, we review ISR antagonists and antagonistic mechanisms employed by picorna- and coronaviruses. Special attention will be given to a recently discovered class of viral antagonists that inhibit the ISR by targeting eIF2B, thereby allowing unabated translation initiation even at exceedingly high levels of phosphorylated eIF2.",

keywords = "Apoptosis, Degradation, Inhibition, Leader protein, Messenger-rna, Mouth-disease virus, Nucleotide exchange, Phosphorylation, Protein-kinase, Translation",

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note = "Funding Information: This work was supported by Marie Sklodowska-Curie Actions (MSCA) Innovative Training Networks (ITN): H2020-MCSA-ITN-2019 (Grant No 813343 ) and OCENW.KLEIN.344 grant from the Dutch Research Council (to FJMvK). Publisher Copyright: {\textcopyright} 2022 The Authors",

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AU - van Kuppeveld, Frank Jm

N1 - Funding Information: This work was supported by Marie Sklodowska-Curie Actions (MSCA) Innovative Training Networks (ITN): H2020-MCSA-ITN-2019 (Grant No 813343 ) and OCENW.KLEIN.344 grant from the Dutch Research Council (to FJMvK). Publisher Copyright: © 2022 The Authors

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KW - Degradation

KW - Inhibition

KW - Leader protein

KW - Messenger-rna

KW - Mouth-disease virus

KW - Nucleotide exchange

KW - Phosphorylation

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M1 - 102254

ER -

Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells

Abstract

Bibliographical note

Keywords

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