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Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses

Influenza A viruses (IAV) modulate host antiviral responses to promote growth and pathogenicity. Here, we examined the multifunctional IAV nonstructural protein 1 (NS1) of influenza A virus to better understand factors that contribute to viral replication efficiency or pathogenicity. In 2009, a pand...

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Autores principales: Huang, Meng-Ting, Zhang, Sen, Wu, Ya-Nan, Li, Wei, Li, Yu-Chang, Zhou, Chang-Shuai, Kang, Xiao-Ping, Jiang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153306/
https://www.ncbi.nlm.nih.gov/pubmed/34068322
http://dx.doi.org/10.3390/v13050905
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author Huang, Meng-Ting
Zhang, Sen
Wu, Ya-Nan
Li, Wei
Li, Yu-Chang
Zhou, Chang-Shuai
Kang, Xiao-Ping
Jiang, Tao
author_facet Huang, Meng-Ting
Zhang, Sen
Wu, Ya-Nan
Li, Wei
Li, Yu-Chang
Zhou, Chang-Shuai
Kang, Xiao-Ping
Jiang, Tao
author_sort Huang, Meng-Ting
collection PubMed
description Influenza A viruses (IAV) modulate host antiviral responses to promote growth and pathogenicity. Here, we examined the multifunctional IAV nonstructural protein 1 (NS1) of influenza A virus to better understand factors that contribute to viral replication efficiency or pathogenicity. In 2009, a pandemic H1N1 IAV (A/California/07/2009 pH1N1) emerged in the human population from swine. Seasonal variants of this virus are still circulating in humans. Here, we compared the sequence of a seasonal variant of this H1N1 influenza virus (A/Urumqi/XJ49/2018(H1N1), first isolated in 2018) with the pandemic strain A/California/07/2009. The 2018 virus harbored amino acid mutations (I123V and N205S) in important functional sites; however, 108R and 189G were highly conserved between A/California/07/2009 and the 2018 variant. To better understand interactions between influenza viruses and the human innate immune system, we generated and rescued seasonal 2009 H1N1 IAV mutants expressing an NS1 protein harboring a dual mutation (R108K/G189D) at these conserved residues and then analyzed its biological characteristics. We found that the mutated NS1 protein exhibited systematic and selective inhibition of cytokine responses via a mechanism that may not involve binding to cleavage and polyadenylation specificity factor 30 (CPSF30). These results highlight the complexity underlying host–influenza NS1 protein interactions.
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spelling pubmed-81533062021-05-27 Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses Huang, Meng-Ting Zhang, Sen Wu, Ya-Nan Li, Wei Li, Yu-Chang Zhou, Chang-Shuai Kang, Xiao-Ping Jiang, Tao Viruses Article Influenza A viruses (IAV) modulate host antiviral responses to promote growth and pathogenicity. Here, we examined the multifunctional IAV nonstructural protein 1 (NS1) of influenza A virus to better understand factors that contribute to viral replication efficiency or pathogenicity. In 2009, a pandemic H1N1 IAV (A/California/07/2009 pH1N1) emerged in the human population from swine. Seasonal variants of this virus are still circulating in humans. Here, we compared the sequence of a seasonal variant of this H1N1 influenza virus (A/Urumqi/XJ49/2018(H1N1), first isolated in 2018) with the pandemic strain A/California/07/2009. The 2018 virus harbored amino acid mutations (I123V and N205S) in important functional sites; however, 108R and 189G were highly conserved between A/California/07/2009 and the 2018 variant. To better understand interactions between influenza viruses and the human innate immune system, we generated and rescued seasonal 2009 H1N1 IAV mutants expressing an NS1 protein harboring a dual mutation (R108K/G189D) at these conserved residues and then analyzed its biological characteristics. We found that the mutated NS1 protein exhibited systematic and selective inhibition of cytokine responses via a mechanism that may not involve binding to cleavage and polyadenylation specificity factor 30 (CPSF30). These results highlight the complexity underlying host–influenza NS1 protein interactions. MDPI 2021-05-13 /pmc/articles/PMC8153306/ /pubmed/34068322 http://dx.doi.org/10.3390/v13050905 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Meng-Ting
Zhang, Sen
Wu, Ya-Nan
Li, Wei
Li, Yu-Chang
Zhou, Chang-Shuai
Kang, Xiao-Ping
Jiang, Tao
Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title_full Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title_fullStr Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title_full_unstemmed Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title_short Dual R108K and G189D Mutations in the NS1 Protein of A/H1N1 Influenza Virus Counteract Host Innate Immune Responses
title_sort dual r108k and g189d mutations in the ns1 protein of a/h1n1 influenza virus counteract host innate immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153306/
https://www.ncbi.nlm.nih.gov/pubmed/34068322
http://dx.doi.org/10.3390/v13050905
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