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. 2021 Jul 13;11:670177. doi: 10.3389/fcimb.2021.670177

Table 1.

Effects of changes of amino acid sites in NS1 on biological characteristics.

IAV NS1 Amino Acid Residue Biological effects Impact on infection Experiment method Reference
A/chicken/China/B1-6/2006(H9N2) X35R
X46R
Losing its RNA silencing suppression activity. Unreported In vitro (Jing et al., 2015)
A/swine/Shanghai/3/2014(H1N1) S42 Regulating the host IFN response by blocking the activation of IRF3 Facilitating virus replication In vitro (Cheng et al., 2018)
A/Duck/Guangxi/12/03(H5N1) P42S Preventing the dsRNA-mediated activation of the NF-κB pathway and the IRF-3 pathway Attenuating virus replication In vitro (Jiao et al., 2008)
A/chicken/Hunan/1/2009 (H5N1) K55E/K66E/C133F Restoring the ability to bind CPSF30 and reduced interferon response activity. Increasing virus titer and replication efficiency In vitro (Li et al., 2018)
Recombined A/Puerto Rico/8/34 (H1N1) I64T Decreasing general inhibition of host protein synthesis by decreasing its interaction with CPSF30 Exhibiting an attenuated phenotype In vivo (DeDiego et al., 2016)
A/Duck/Hubei/2004/L-1(H5N1) Y84F Abolishing NS1-mediated downregulation of IFN-inducible STAT phosphorylation, and surface IFNAR1 expression Reducing lung viral titers and increased lung ISG expression In vivo (Wang et al., 2017)
A/Hong Kong/156/97(H5N1) D92E Activating phosphorylation of NS1 Unreported In silico (Li and Wang, 2007)
A/quail/Hong Kong/G1/97(H9N2) L103F/I106M/P114/G125D/N139D Restoring CPSF30 binding capacity and inhibiting host gene expression Unreported In vitro (Rodriguez et al., 2018)
A/Hong Kong/156/1997(H5N1) F103L
M106I
Increasing the ability of IFN antagonism, altering RIG-I and CPSF30 host factor binding ability Increasing viral replication in mouse lungs In vivo (Dankar et al., 2013)
A/Hong Kong/1/68(H3N2) F103L
M106I
Increasing tropism and virulence in mouse lungs In vivo (Dankar et al., 2011)
Recombined A/Shanghai/1/2013 (H7N9) I106M Restoring the ability of CPSF30 binding and that of block host gene expression Showing enhanced replication and virulence In vivo (Ayllon et al., 2014)
Recombined A/Puerto Rico/8/34 (H1N1) A171Y Decreasing expression of IFN and ISGs Unknown In vitro (Plant et al., 2017)
A/Udorn/72(H1N1) G184R An unknown mechanism independent of overactivation of the host IFN response or to enhanced sensitivity of these viruses to the antiviral effect of PKR Remarkable attenuation of virulence In vivo (Steidle et al., 2010)
A/canine/NY/dog23/2009(H3N8) K186E Introducing both the NS1-CPSF30 interaction and ISGs gene expression inhibition Unreported In vitro (Nogales et al., 2017)
(Chauché et al., 2018)
Recombined A/Puerto Rico/8/34 (H1N1) D189N Impairing the ability of the NS1 protein to inhibit general gene expression Attenuating virulence In vitro
In vivo
(Nogales et al., 2017)
V194I Demonstrating a temperature-sensitive phenotype Attenuating virulence more than D189N