Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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
_version_ 1783484970377936896
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
work_keys_str_mv AT hungsujhen geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT hsuyinmei geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT huangshengwen geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT tsaihueypin geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT leeleoyiyang geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT hurtaeronc geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT barriang geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT shihshinru geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation
AT wangjenren geneticvariationson31and450residuesofinfluenzaanucleoproteinaffectviralreplicationandtranslation