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Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation
BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus ev...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943894/ https://www.ncbi.nlm.nih.gov/pubmed/31906961 http://dx.doi.org/10.1186/s12929-019-0612-z |
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author | Hung, Su-Jhen Hsu, Yin-Mei Huang, Sheng-Wen Tsai, Huey-Pin Lee, Leo Yi Yang Hurt, Aeron C. Barr, Ian G. Shih, Shin-Ru Wang, Jen-Ren |
author_facet | Hung, Su-Jhen Hsu, Yin-Mei Huang, Sheng-Wen Tsai, Huey-Pin Lee, Leo Yi Yang Hurt, Aeron C. Barr, Ian G. Shih, Shin-Ru Wang, Jen-Ren |
author_sort | Hung, Su-Jhen |
collection | PubMed |
description | BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention. |
format | Online Article Text |
id | pubmed-6943894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69438942020-01-07 Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation Hung, Su-Jhen Hsu, Yin-Mei Huang, Sheng-Wen Tsai, Huey-Pin Lee, Leo Yi Yang Hurt, Aeron C. Barr, Ian G. Shih, Shin-Ru Wang, Jen-Ren J Biomed Sci Research BACKGROUND: Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. METHODS: To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. RESULTS: The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo. CONCLUSIONS: These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention. BioMed Central 2020-01-06 /pmc/articles/PMC6943894/ /pubmed/31906961 http://dx.doi.org/10.1186/s12929-019-0612-z Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Hung, Su-Jhen Hsu, Yin-Mei Huang, Sheng-Wen Tsai, Huey-Pin Lee, Leo Yi Yang Hurt, Aeron C. Barr, Ian G. Shih, Shin-Ru Wang, Jen-Ren Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title | Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title_full | Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title_fullStr | Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title_full_unstemmed | Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title_short | Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation |
title_sort | genetic variations on 31 and 450 residues of influenza a nucleoprotein affect viral replication and translation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943894/ https://www.ncbi.nlm.nih.gov/pubmed/31906961 http://dx.doi.org/10.1186/s12929-019-0612-z |
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