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

Yanxia Huang, Qinyu Peng, Xu Tian, Cancan Chen, Xuanfeng Zhu, Changbai Huang, Zhiting Huo, Yang Liu, Chao Yang (), Chao Liu () and Ping Zhang ()
Additional contact information
Yanxia Huang: Ministry of Education
Qinyu Peng: Ministry of Education
Xu Tian: Ministry of Education
Cancan Chen: First Affiliated Hospital of Sun Yat-sen University
Xuanfeng Zhu: Ministry of Education
Changbai Huang: Ministry of Education
Zhiting Huo: Ministry of Education
Yang Liu: Li Ka Shing Faculty of Medicine, The University of Hong Kong
Chao Yang: First Affiliated Hospital of Sun Yat-sen University
Chao Liu: Ministry of Education
Ping Zhang: Ministry of Education

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44580-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44580-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44580-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().