Influenza A Nonstructural Protein (NS1)

Influenza A Nonstructural Protein (NS1)

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.
Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 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.

Modulation by symbiont of host intracellular transportManual Assertion Based On ExperimentIDA:BHF-UCL
Modulation by virus of host transcriptionManual Assertion Based On ExperimentIDA:BHF-UCL
Suppression by symbiont of host innate immune responseManual Assertion Based On ExperimentIDA:BHF-UCL
Suppression by virus of host cytokine productionManual Assertion Based On ExperimentIDA:BHF-UCL
Suppression by virus of host mRNA processingIEA:UniProtKB-KW
Suppression by virus of host PKR signalingIEA:UniProtKB-KW
Suppression by virus of host type I interferon-mediated signaling pathwayIEA:UniProtKB-KW
Suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activityIEA:UniProtKB-KW

Host nucleus; Host cytoplasm. In uninfected, transfected cells, NS1 is localized in the nucleus. Only in virus infected cells, the nuclear export signal is unveiled, presumably by a viral protein, and a fraction of NS1 is exported in the cytoplasm.

Upon interferon induction, ISGylated via host HERC5; this results in the impairment of NS1 interaction with RNA targets due to its inability to form homodimers and to interact with host EIF2AK2/PKR.