Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: mBio

Bandnummer: 11

Heftnummer: 4

ISSN: 2150-7511

Open Access Status: Gold

DOI Link: https://doi.org/10.1128/mBio.00976-20

Verlag: American Society for Microbiology

Abstract: 

RNA-activated protein kinase (PKR) is a major innate immune factor that senses viral double-stranded RNA (dsRNA) and phosphorylates eukaryotic initiation factor (eIF) 2 alpha. Phosphorylation of the a subunit converts the eIF2 alpha beta gamma complex into a stoichiometric inhibitor of eukaryotic initiation factor eIF2B, thus halting mRNA translation. To escape this protein synthesis shutoff, viruses have evolved countermechanisms such as dsRNA sequestration, eIF-independent translation by an internal ribosome binding site, degradation of PKR, or dephosphorylation of PKR or of phospho-eIF2 alpha. Here, we report that sandfly fever Sicilian phlebovirus (SFSV) confers such a resistance without interfering with PKR activation or eIF2 alpha phosphorylation. Rather, SFSV expresses a nonstructural protein termed NSs that strongly binds to eIF2B. Although NSs still allows phosphoe-IF2 alpha binding to eIF2B, protein synthesis and virus replication are unhindered. Hence, SFSV encodes a unique PKR antagonist that acts by rendering eIF2B resistant to the inhibitory action of bound phospho-eIF2 alpha.

Harvard-Zitierstil: Wuerth, J., Habjan, M., Kainulainen, M., Berisha, B., Bertheloot, D., Superti-Furga, G., et al. (2020) eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition, mBio, 11(4), Article e00976-20. https://doi.org/10.1128/mBio.00976-20

APA-Zitierstil: Wuerth, J., Habjan, M., Kainulainen, M., Berisha, B., Bertheloot, D., Superti-Furga, G., Pichlmair, A., & Weber, F. (2020). eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition. mBio. 11(4), Article e00976-20. https://doi.org/10.1128/mBio.00976-20