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hnRNPA1 impedes snakehead vesiculovirus replication via competitively disrupting viral phosphoprotein-nucleoprotein interaction and degrading viral phosphoprotein

Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays an important role in regulating the replication of many viruses. However, it remains elusive whether and how hnRNPA1 regulates fish virus replication. In this study, the effects of twelve hnRNPs on the replication of snakehead vesiculovirus...

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Published in:Virulence 2023-12, Vol.14 (1), p.2196847-2196847
Main Authors: Liu, An-Qi, Qin, Xiangmou, Wu, Hui, Feng, Hao, Zhang, Yong-An, Tu, Jiagang
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Wu, Hui
Feng, Hao
Zhang, Yong-An
Tu, Jiagang
description Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays an important role in regulating the replication of many viruses. However, it remains elusive whether and how hnRNPA1 regulates fish virus replication. In this study, the effects of twelve hnRNPs on the replication of snakehead vesiculovirus (SHVV) were screened. Three hnRNPs, one of which was hnRNPA1, were identified as anti-SHVV factors. Further verification showed that knockdown of hnRNPA1 promoted, while overexpression of hnRNPA1 inhibited, SHVV replication. SHVV infection reduced the expression level of hnRNPA1 and induced the nucleocytoplasmic shuttling of hnRNPA1. Besides, we found that hnRNPA1 interacted with the viral phosphoprotein (P) via its glycine-rich domain, but not with the viral nucleoprotein (N) or large protein (L). The hnRNPA1-P interaction competitively disrupted the viral P-N interaction. Moreover, we found that overexpression of hnRNPA1 enhanced the polyubiquitination of the P protein and degraded it through proteasomal and lysosomal pathways. This study will help understanding the function of hnRNPA1 in the replication of single-stranded negative-sense RNA viruses and providing a novel antiviral target against fish rhabdoviruses.
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However, it remains elusive whether and how hnRNPA1 regulates fish virus replication. In this study, the effects of twelve hnRNPs on the replication of snakehead vesiculovirus (SHVV) were screened. Three hnRNPs, one of which was hnRNPA1, were identified as anti-SHVV factors. Further verification showed that knockdown of hnRNPA1 promoted, while overexpression of hnRNPA1 inhibited, SHVV replication. SHVV infection reduced the expression level of hnRNPA1 and induced the nucleocytoplasmic shuttling of hnRNPA1. Besides, we found that hnRNPA1 interacted with the viral phosphoprotein (P) via its glycine-rich domain, but not with the viral nucleoprotein (N) or large protein (L). The hnRNPA1-P interaction competitively disrupted the viral P-N interaction. Moreover, we found that overexpression of hnRNPA1 enhanced the polyubiquitination of the P protein and degraded it through proteasomal and lysosomal pathways. This study will help understanding the function of hnRNPA1 in the replication of single-stranded negative-sense RNA viruses and providing a novel antiviral target against fish rhabdoviruses.</description><identifier>ISSN: 2150-5594</identifier><identifier>EISSN: 2150-5608</identifier><identifier>DOI: 10.1080/21505594.2023.2196847</identifier><identifier>PMID: 37005771</identifier><language>eng</language><publisher>United States: Taylor &amp; Francis</publisher><subject>Animals ; Fishes ; Heterogeneous Nuclear Ribonucleoprotein A1 - genetics ; HnRNPA1 ; Nucleocytoplasmic shuttling ; Nucleoproteins - metabolism ; P protein ; Phosphoproteins - metabolism ; Replication ; Rhabdoviridae Infections - metabolism ; Snakehead vesiculovirus (SHVV) ; Vesiculovirus - genetics ; Vesiculovirus - metabolism ; Virus Replication</subject><ispartof>Virulence, 2023-12, Vol.14 (1), p.2196847-2196847</ispartof><rights>2023 The Author(s). 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Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Virulence</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, An-Qi</au><au>Qin, Xiangmou</au><au>Wu, Hui</au><au>Feng, Hao</au><au>Zhang, Yong-An</au><au>Tu, Jiagang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>hnRNPA1 impedes snakehead vesiculovirus replication via competitively disrupting viral phosphoprotein-nucleoprotein interaction and degrading viral phosphoprotein</atitle><jtitle>Virulence</jtitle><addtitle>Virulence</addtitle><date>2023-12-31</date><risdate>2023</risdate><volume>14</volume><issue>1</issue><spage>2196847</spage><epage>2196847</epage><pages>2196847-2196847</pages><issn>2150-5594</issn><eissn>2150-5608</eissn><abstract>Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays an important role in regulating the replication of many viruses. 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subjects Animals
Fishes
Heterogeneous Nuclear Ribonucleoprotein A1 - genetics
HnRNPA1
Nucleocytoplasmic shuttling
Nucleoproteins - metabolism
P protein
Phosphoproteins - metabolism
Replication
Rhabdoviridae Infections - metabolism
Snakehead vesiculovirus (SHVV)
Vesiculovirus - genetics
Vesiculovirus - metabolism
Virus Replication
title hnRNPA1 impedes snakehead vesiculovirus replication via competitively disrupting viral phosphoprotein-nucleoprotein interaction and degrading viral phosphoprotein
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