tetano
Editor, Senior Moderator
Cell Microbiol. 2016 Jul 4. doi: 10.1111/cmi.12643. [Epub ahead of print]
[h=1]Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I.[/h] Zheng W[SUP]1,[/SUP][SUP]2[/SUP], Cao S[SUP]1[/SUP], Chen C[SUP]1,[/SUP][SUP]2[/SUP], Li J[SUP]1[/SUP], Zhang S[SUP]1[/SUP], Jiang J[SUP]1,[/SUP][SUP]3[/SUP], Niu Y[SUP]1,[/SUP][SUP]2[/SUP], Fan W[SUP]1[/SUP], Li Y[SUP]1[/SUP], Bi Y[SUP]1[/SUP], Sun L[SUP]1[/SUP], Gao GF[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Liu W[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus evades host antiviral defense through hijacking innate immunity by its nonstructural 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 experiments. In further study, the T80E mutant decreased the binding capacity 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 RNA and retinoic acid-induced gene 1 protein (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.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza A virus; NS1; interferon; phosphorylation; viral replication
PMID: 27376632 DOI: 10.1111/cmi.12643
[PubMed - as supplied by publisher]
[h=1]Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I.[/h] Zheng W[SUP]1,[/SUP][SUP]2[/SUP], Cao S[SUP]1[/SUP], Chen C[SUP]1,[/SUP][SUP]2[/SUP], Li J[SUP]1[/SUP], Zhang S[SUP]1[/SUP], Jiang J[SUP]1,[/SUP][SUP]3[/SUP], Niu Y[SUP]1,[/SUP][SUP]2[/SUP], Fan W[SUP]1[/SUP], Li Y[SUP]1[/SUP], Bi Y[SUP]1[/SUP], Sun L[SUP]1[/SUP], Gao GF[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Liu W[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus evades host antiviral defense through hijacking innate immunity by its nonstructural 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 experiments. In further study, the T80E mutant decreased the binding capacity 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 RNA and retinoic acid-induced gene 1 protein (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.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza A virus; NS1; interferon; phosphorylation; viral replication
PMID: 27376632 DOI: 10.1111/cmi.12643
[PubMed - as supplied by publisher]