Threonine 80 phosphorylation of non‐structural protein 1 regulates the replication of influenza A virus by reducing the binding affinity with RIG‐I
Influenza A virus evades host antiviral defense through hijacking innate immunity by its non-structural protein 1 (NS1). By using mass spectrometry, threonine 80 (T80) was identified as a novel phosphorylated residue in the NS1 of the influenza virus A/WSN/1933(H1N1). By generating recombinant influenza viruses encoding NS1 T80 mutants, the roles of this phosphorylation site were characterized during viral replication. The T80E (phosphomimetic) mutant attenuated virus replication, whereas the T80A (non-phosphorylatable) mutant did not. Similar phenotypes were observed for these mutants in a mouse model experiment. In further study, the T80E mutant decreased the bindingcapacity between NS1 and viral nucleoprotein (NP), leading to impaired viral ribonucleoprotein (vRNP)-mediated viral transcription. The T80E mutant was also unable to inhibit interferon (IFN) production by reducing the binding affinity between NS1 and retinoic acid-induced gene 1protein (RIG-I), causing attenuation of virus replication. Taken together, the present study reveals that T80 phosphorylation of NS1 reduced influenza virus replication through controlling RIG-I-mediated IFN production and vRNP activity.
Authors: Zheng W1, Cao S1, Chen C1,2, Li J1, Zhang S1, Jiang J1,3, Niu Y1,2, Fan W1, Li Y1, Bi Y1, Gao GF1,2,4,5, Sun L1, Liu W1.
Influence Factor: 4.5539
Citation: Cellular Microbiology 19, e12643 (2017).