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Article: Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1

TitleNuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1
Authors
Issue Date1-Dec-2024
PublisherNature Research
Citation
Nature Communications, 2024, v. 15, n. 1 How to Cite?
Abstract

Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain protein 2 (SUN2) linking cytoskeleton and nucleoskeleton in the flavivirus replication. CRISPR/Cas9-mediated knockout of SUN2, but not SUN1, significantly reduces the replication of Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV). In contrast, SUN2 does not affect the infection of non-flaviviridae RNA viruses. All three regions of SUN2 are required for its proviral effect. Mechanistically, SUN2 facilitates rearrangement of cytoskeleton and formation of replication organelles induced by viral infection, and hence promotes viral RNA synthesis. SUN2 is required for the interaction between cytoskeleton actin and ZIKV nonstructural protein 1 (NS1). Expression of dominant negative Nesprin-1 and Nesprin-2, which connect SUN2 to cytoskeleton proteins, alleviates the interaction between actin and NS1 and reduces viral replication levels. In a neonatal mouse infection model, SUN2 knockout dramatically alleviates the in vivo ZIKV replication and development of neuropathology. This work elucidates that recruitment of cytoskeleton proteins by flavivirus is coordinated by nuclear membrane proteins SUN2 and Nesprins, providing evidence for a link between nuclear membrane proteins and flavivirus infection.


Persistent Identifierhttp://hdl.handle.net/10722/339701
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, Yanxia-
dc.contributor.authorPeng, Qinyu-
dc.contributor.authorTian, Xu-
dc.contributor.authorChen, Cancan-
dc.contributor.authorZhu, Xuanfeng-
dc.contributor.authorHuang, Changbai-
dc.contributor.authorHuo, Zhiting-
dc.contributor.authorLiu, Yang-
dc.contributor.authorYang, Chao-
dc.contributor.authorLiu, Chao-
dc.contributor.authorZhang, Ping-
dc.date.accessioned2024-03-11T10:38:41Z-
dc.date.available2024-03-11T10:38:41Z-
dc.date.issued2024-12-01-
dc.identifier.citationNature Communications, 2024, v. 15, n. 1-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/339701-
dc.description.abstract<p> <span>Cytoskeleton is extensively recruited by flaviviruses for their infection. In this study, we uncovered an essential role of a nuclear membrane protein, SAD1/UNC84 domain protein 2 (SUN2) linking cytoskeleton and nucleoskeleton in the flavivirus replication. CRISPR/Cas9-mediated knockout of SUN2, but not SUN1, significantly reduces the replication of Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV). In contrast, SUN2 does not affect the infection of non-flaviviridae RNA viruses. All three regions of SUN2 are required for its proviral effect. Mechanistically, SUN2 facilitates rearrangement of cytoskeleton and formation of replication organelles induced by viral infection, and hence promotes viral RNA synthesis. SUN2 is required for the interaction between cytoskeleton actin and ZIKV nonstructural protein 1 (NS1). Expression of dominant negative Nesprin-1 and Nesprin-2, which connect SUN2 to cytoskeleton proteins, alleviates the interaction between actin and NS1 and reduces viral replication levels. In a neonatal mouse infection model, SUN2 knockout dramatically alleviates the in vivo ZIKV replication and development of neuropathology. This work elucidates that recruitment of cytoskeleton proteins by flavivirus is coordinated by nuclear membrane proteins SUN2 and Nesprins, providing evidence for a link between nuclear membrane proteins and flavivirus infection.</span> <br></p>-
dc.languageeng-
dc.publisherNature Research-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleNuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-023-44580-6-
dc.identifier.scopuseid_2-s2.0-85181463474-
dc.identifier.volume15-
dc.identifier.issue1-
dc.identifier.eissn2041-1723-
dc.identifier.isiWOS:001136827200001-
dc.identifier.issnl2041-1723-

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