Abstract
BackgroundThe influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response. In the avian influenza virus or human influenza virus, specific amino acids of NS1 have been shown to be important for the virus to antagonize host antiviral defenses and promote viral replication. However, little research has been reported regarding the swine influenza virus (SIV) NS1 protein.MethodsTo study the effects of the key amino acids of NS1, we rescued NS1 mutants (S42P, D92E, and S42P/D92E) of the A/swine/Shanghai/3/2014(H1N1) strain and compared their replication ability and cytokine production as well as the intracellular localization in cultured cells.ResultsWe found that the S42P and D92E mutation displayed no changes on NS1 nuclear localization. The S42P (but not D92E) mutation suppressed protein synthesis and reduced virus growth properties, and there was an inability to antagonize host cell interferon production and IRF3 activation, which led to high levels of IFN-α and IFN-β production.ConclusionWe conclude that the S42 residue of the NS1 of the A/swine/Shanghai/3/2014(H1N1) strain is the key amino acid in regulating the host IFN response by blocking the activation of IRF3 and thus facilitates virus replication.
Highlights
The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response
This work will be useful for a further understanding of how the amino acid mutations influence the function of the NS1 protein and the interaction between H1N1 swine influenza virus (SIV) and the host innate immune responses
These results indicated that rSIV NS1 S42P, rSIV NS1 D92E and rSIV NS1 S42P/ D92E viruses were successfully rescued
Summary
The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response. In the avian influenza virus or human influenza virus, specific amino acids of NS1 have been shown to be important for the virus to antagonize host antiviral defenses and promote viral replication. Non-structural protein 1 (NS1) is a virulence factor of the influenza virus and is expressed in the nucleus and cytoplasm of host cells during infection. Functional as a dimer, the NS1 comprises an N-terminal dsRNAbinding domain and a C-terminal protein-binding effector domain [5] It can interact with a diverse range of cellular factors to antagonize host antiviral defenses and promote viral replication [6]. Mechanisms involved in the NS1 protein’s ability to counteract innate immune responses include the inhibition of cellular premRNA splicing and polyadenylation [7], which blocks posttranscriptional RNA processing and nuclear export, decreases retinoic acid-inducible gene 1 (RIG-I) activation through inhibition of tripartite motif family 25
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