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An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells
Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic s...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364394/ https://www.ncbi.nlm.nih.gov/pubmed/28323816 http://dx.doi.org/10.1038/ncomms14751 |
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author | Huang, Xiaofeng Zheng, Min Wang, Pui Mok, Bobo Wing-Yee Liu, Siwen Lau, Siu-Ying Chen, Pin Liu, Yen-Chin Liu, Honglian Chen, Yixin Song, Wenjun Yuen, Kwok-Yung Chen, Honglin |
author_facet | Huang, Xiaofeng Zheng, Min Wang, Pui Mok, Bobo Wing-Yee Liu, Siwen Lau, Siu-Ying Chen, Pin Liu, Yen-Chin Liu, Honglian Chen, Yixin Song, Wenjun Yuen, Kwok-Yung Chen, Honglin |
author_sort | Huang, Xiaofeng |
collection | PubMed |
description | Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2–ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells. |
format | Online Article Text |
id | pubmed-5364394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53643942017-04-11 An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells Huang, Xiaofeng Zheng, Min Wang, Pui Mok, Bobo Wing-Yee Liu, Siwen Lau, Siu-Ying Chen, Pin Liu, Yen-Chin Liu, Honglian Chen, Yixin Song, Wenjun Yuen, Kwok-Yung Chen, Honglin Nat Commun Article Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2–ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells. Nature Publishing Group 2017-03-21 /pmc/articles/PMC5364394/ /pubmed/28323816 http://dx.doi.org/10.1038/ncomms14751 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Huang, Xiaofeng Zheng, Min Wang, Pui Mok, Bobo Wing-Yee Liu, Siwen Lau, Siu-Ying Chen, Pin Liu, Yen-Chin Liu, Honglian Chen, Yixin Song, Wenjun Yuen, Kwok-Yung Chen, Honglin An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title | An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title_full | An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title_fullStr | An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title_full_unstemmed | An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title_short | An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells |
title_sort | ns-segment exonic splicing enhancer regulates influenza a virus replication in mammalian cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364394/ https://www.ncbi.nlm.nih.gov/pubmed/28323816 http://dx.doi.org/10.1038/ncomms14751 |
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