5bxz

Structural highlights

Function

H6QM79_I09A8 Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated RIGI ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113]

References

1. ↑ Turkington HL, Juozapaitis M, Kerry PS, Aydillo T, Ayllon J, Garcia-Sastre A, Schwemmle M, Hale BG. Novel Bat Influenza Virus NS1 Proteins Bind Double-Stranded RNA and Antagonize Host Innate Immunity. J Virol. 2015 Aug 5. pii: JVI.01430-15. PMID:26246567 doi:http://dx.doi.org/10.1128/JVI.01430-15