eIF2B-capturing viral protein NSs suppresses the integrated stress response
書誌事項
- 公開日
- 2021-06-08
- 資源種別
- journal article
- DOI
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- 10.1101/2021.06.07.447466
- 10.1038/s41467-021-27337-x
- 公開者
- openRxiv
説明
<jats:title>SUMMARY</jats:title> <jats:p>Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotides on unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. Our cryo-electron microscopy (cryo-EM) analysis revealed that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B exhibits normal nucleotide exchange activity even in the presence of eIF2(αP). A genome-wide ribosome profiling analysis clarified that SFSV NSs in human cultured cells attenuates the ISR. Furthermore, SFSV NSs exhibited neuroprotective effects against the ISR-inducing stress. Since the ISR inhibition is beneficial in various neurological disease models, SFSV NSs is promising as a therapeutic ISR inhibitor.</jats:p>
収録刊行物
-
- Nature Communications
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Nature Communications 12 (1), 1-, 2021-06-08
openRxiv