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Transportin-3 Facilitates Uncoating of Influenza A Virus

Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infec...

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Autores principales: Zou, Jiahui, Yu, Luyao, Zhu, Yinxing, Yang, Shuaike, Zhao, Jiachang, Zhao, Yaxin, Jiang, Meijun, Xie, Shengsong, Liu, Hailong, Zhao, Changzhi, Zhou, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027869/
https://www.ncbi.nlm.nih.gov/pubmed/35456945
http://dx.doi.org/10.3390/ijms23084128
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author Zou, Jiahui
Yu, Luyao
Zhu, Yinxing
Yang, Shuaike
Zhao, Jiachang
Zhao, Yaxin
Jiang, Meijun
Xie, Shengsong
Liu, Hailong
Zhao, Changzhi
Zhou, Hongbo
author_facet Zou, Jiahui
Yu, Luyao
Zhu, Yinxing
Yang, Shuaike
Zhao, Jiachang
Zhao, Yaxin
Jiang, Meijun
Xie, Shengsong
Liu, Hailong
Zhao, Changzhi
Zhou, Hongbo
author_sort Zou, Jiahui
collection PubMed
description Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease.
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spelling pubmed-90278692022-04-23 Transportin-3 Facilitates Uncoating of Influenza A Virus Zou, Jiahui Yu, Luyao Zhu, Yinxing Yang, Shuaike Zhao, Jiachang Zhao, Yaxin Jiang, Meijun Xie, Shengsong Liu, Hailong Zhao, Changzhi Zhou, Hongbo Int J Mol Sci Article Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease. MDPI 2022-04-08 /pmc/articles/PMC9027869/ /pubmed/35456945 http://dx.doi.org/10.3390/ijms23084128 Text en © 2022 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
Zou, Jiahui
Yu, Luyao
Zhu, Yinxing
Yang, Shuaike
Zhao, Jiachang
Zhao, Yaxin
Jiang, Meijun
Xie, Shengsong
Liu, Hailong
Zhao, Changzhi
Zhou, Hongbo
Transportin-3 Facilitates Uncoating of Influenza A Virus
title Transportin-3 Facilitates Uncoating of Influenza A Virus
title_full Transportin-3 Facilitates Uncoating of Influenza A Virus
title_fullStr Transportin-3 Facilitates Uncoating of Influenza A Virus
title_full_unstemmed Transportin-3 Facilitates Uncoating of Influenza A Virus
title_short Transportin-3 Facilitates Uncoating of Influenza A Virus
title_sort transportin-3 facilitates uncoating of influenza a virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027869/
https://www.ncbi.nlm.nih.gov/pubmed/35456945
http://dx.doi.org/10.3390/ijms23084128
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