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

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.

Automated summary

When viruses enter host cells, they face a strong immune defense. The integrated stress response (ISR) is a well-known antiviral pathway, where eukaryotic initiation factor 2 (eIF2) becomes phosphorylated, inhibiting eIF2B and causing global translational arrest. Some viruses have developed antagonistic mechanisms against ISR, including a recently discovered class of viral antagonists that target eIF2B, allowing continued translation initiation even at high levels of phosphorylated eIF2.