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Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner

BACKGROUND: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a key player in inhibiting antiviral response in host cells, thereby facilitating its replication. However, other roles of NS1, which are independent of antagonising host cells’ antiviral response, are less characterised. M...

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Autores principales: Sha, Tim Wai, Weber, Michaela, Kasumba, Dacquin M., Noda, Takeshi, Nakano, Masahiro, Kato, Hiroki, Fujita, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367362/
https://www.ncbi.nlm.nih.gov/pubmed/32677963
http://dx.doi.org/10.1186/s12985-020-01357-3
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author Sha, Tim Wai
Weber, Michaela
Kasumba, Dacquin M.
Noda, Takeshi
Nakano, Masahiro
Kato, Hiroki
Fujita, Takashi
author_facet Sha, Tim Wai
Weber, Michaela
Kasumba, Dacquin M.
Noda, Takeshi
Nakano, Masahiro
Kato, Hiroki
Fujita, Takashi
author_sort Sha, Tim Wai
collection PubMed
description BACKGROUND: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a key player in inhibiting antiviral response in host cells, thereby facilitating its replication. However, other roles of NS1, which are independent of antagonising host cells’ antiviral response, are less characterised. METHODS: To investigate these unidentified roles, we used a recombinant virus, which lacks NS1 expression, and observed its phenotypes during the infection of antiviral defective cells (RIG-I KO cells) in the presence or absence of exogeneous NS1. Moreover, we used virus-like particle (VLP) production system to further support our findings. RESULTS: Our experiments demonstrated that IAV deficient in NS1 replicates less efficiently than wild-type IAV in RIG-I KO cells and this replication defect was complemented by ectopic expression of NS1. As suggested previously, NS1 is incorporated in the virion and participates in the regulation of viral transcription and translation. Using the VLP production system, in which minigenome transcription or viral protein production was unaffected by NS1, we demonstrated that NS1 facilitates viral genome packaging into VLP, leading to efficient minigenome transfer by VLP. Furthermore, the incorporation of NS1 and the minigenome into VLP were impaired by introducing a point mutation (R38A) in the double stranded RNA-binding domain of NS1. CONCLUSION: These results suggest a novel function of NS1 in improving genome packaging in a dsRNA binding-dependent manner. Taken together, NS1 acts as an essential pro-viral regulator, not only by antagonizing host immunity but also by facilitating viral replication and genome packaging.
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spelling pubmed-73673622020-07-20 Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner Sha, Tim Wai Weber, Michaela Kasumba, Dacquin M. Noda, Takeshi Nakano, Masahiro Kato, Hiroki Fujita, Takashi Virol J Research BACKGROUND: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a key player in inhibiting antiviral response in host cells, thereby facilitating its replication. However, other roles of NS1, which are independent of antagonising host cells’ antiviral response, are less characterised. METHODS: To investigate these unidentified roles, we used a recombinant virus, which lacks NS1 expression, and observed its phenotypes during the infection of antiviral defective cells (RIG-I KO cells) in the presence or absence of exogeneous NS1. Moreover, we used virus-like particle (VLP) production system to further support our findings. RESULTS: Our experiments demonstrated that IAV deficient in NS1 replicates less efficiently than wild-type IAV in RIG-I KO cells and this replication defect was complemented by ectopic expression of NS1. As suggested previously, NS1 is incorporated in the virion and participates in the regulation of viral transcription and translation. Using the VLP production system, in which minigenome transcription or viral protein production was unaffected by NS1, we demonstrated that NS1 facilitates viral genome packaging into VLP, leading to efficient minigenome transfer by VLP. Furthermore, the incorporation of NS1 and the minigenome into VLP were impaired by introducing a point mutation (R38A) in the double stranded RNA-binding domain of NS1. CONCLUSION: These results suggest a novel function of NS1 in improving genome packaging in a dsRNA binding-dependent manner. Taken together, NS1 acts as an essential pro-viral regulator, not only by antagonizing host immunity but also by facilitating viral replication and genome packaging. BioMed Central 2020-07-16 /pmc/articles/PMC7367362/ /pubmed/32677963 http://dx.doi.org/10.1186/s12985-020-01357-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sha, Tim Wai
Weber, Michaela
Kasumba, Dacquin M.
Noda, Takeshi
Nakano, Masahiro
Kato, Hiroki
Fujita, Takashi
Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title_full Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title_fullStr Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title_full_unstemmed Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title_short Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner
title_sort influenza a virus ns1 optimises virus infectivity by enhancing genome packaging in a dsrna-binding dependent manner
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367362/
https://www.ncbi.nlm.nih.gov/pubmed/32677963
http://dx.doi.org/10.1186/s12985-020-01357-3
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