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Cell Microbiol. 2016 Jul 4. doi: 10.1111/cmi.12643. [Epub ahead of print]
Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I.
Zheng W1,2, Cao S1, Chen C1,2, Li J1, Zhang S1, Jiang J1,3, Niu Y1,2, Fan W1, Li Y1, Bi Y1, Sun L1, Gao GF1,2,4,5, Liu W1,2.
Author information
Abstract
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.
KEYWORDS:
Influenza A virus; NS1; interferon; phosphorylation; viral replication
PMID: 27376632 DOI: 10.1111/cmi.12643
[PubMed - as supplied by publisher]
Threonine 80 Phosphorylation of Non-Structural Protein NS1 Regulates the Replication of Influenza A Virus by Reducing the Binding Affinity with RIG-I.
Zheng W1,2, Cao S1, Chen C1,2, Li J1, Zhang S1, Jiang J1,3, Niu Y1,2, Fan W1, Li Y1, Bi Y1, Sun L1, Gao GF1,2,4,5, Liu W1,2.
Author information
Abstract
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.
KEYWORDS:
Influenza A virus; NS1; interferon; phosphorylation; viral replication
PMID: 27376632 DOI: 10.1111/cmi.12643
[PubMed - as supplied by publisher]