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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.

SUBMITTER: Aloise C 

PROVIDER: S-EPMC9515345 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Aloise Chiara C   Schipper Jelle G JG   de Groot Raoul J RJ   van Kuppeveld Frank Jm FJ  

Current opinion in immunology 20220928


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 ensue  ...[more]

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