Cardiovirus-Mediated PKR inhibition results from nucleocytoplasmic trafficking disruption.

ABSTRACT: Eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2), known as PKR, is a key antiviral kinase activated by double-stranded RNA (dsRNA) typically produced during viral replication. Upon activation, PKR phosphorylates eIF2α, leading to the inhibition of translation and viral replication. However, many viruses have evolved mechanisms to counteract PKR activity. In Cardioviruses, the leader protein (L), a short peptide cleaved from the N-terminus of the viral polyprotein, not only inhibits PKR but also blocks interferon production and disrupts nucleocytoplasmic trafficking (NCT). L disrupts NCT by recruiting host RSK kinases to the nuclear pore complex (NPC), where RSK phosphorylates FG-nucleoporins, thereby impairing NCT. L mutations that affect NCT disruption also impact PKR i

SUBMITTER: Milcamps R 

PROVIDER: S-EPMC12747429 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature