Virus Details


VHFID10033

Host Factor Information

Gene Name SUN2
HF Protein Name Sad1 and UNC84 domain-containing protein 2
HF Function
Uniprot ID Q9UH99
Protein Sequence View Fasta Sequence
NCBI Gene ID 25777
Host Factor (HF) Name in Paper SUN2
Gene synonyms FRIGG KIAA0668 RAB5IP UNC84B
Ensemble Gene ID ENSG00000100242
Ensemble Transcript ENST00000405018.5 [Q9UH99-2];ENST00000405510.5 [Q9UH99-1];ENST00000406622.5 [Q9UH99-1];ENST00000689035.1 [Q9UH99-1]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000781, GO:0000794, GO:0005521, GO:0005635, GO:0005637, GO:0007052, GO:0007097, GO:0008017, GO:0010008, GO:0021817, GO:0030335, GO:0031022, GO:0031965, GO:0034993, GO:0042802, GO:0043495, GO:0051321, GO:0051642, GO:0090292, GO:0140444,
MINT ID Q9UH99
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 613569
PANTHER ID PTHR12911;PTHR12911:SF22
PDB ID(s) 3UNP, 4DXR, 4DXS, 4DXT, 4FI9, 6WMD, 6WME, 6WMF, 6WMG,
pfam ID PF18580, PF07738,
Drug Bank ID N.A.,
ChEMBL ID N.A.
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Japanese encephalitis virus
Virus Short Name JEV
Order Amarillovirales
Virus Family Flaviviridae
Virus Subfamily N.A.
Genus Flavivirus
Species Japanese encephalitis virus
Host Vertebrates
Cell Tropism Neurons
Associated Disease Encephalitis
Mode of Transmission Sexual contact, blood, breast feeding
VIPR DB link https://www.viprbrc.org/brc/vipr_search.do?species=Japanese_encephalitis_virus
ICTV DB link https://ictv.global/report/183/flaviviridae
Virus Host DB link

Publication Information

Paper Title Nuclear membrane protein SUN2 promotes replication of flaviviruses through modulating cytoskeleton reorganization mediated by NS1
Author's Name Yanxia Huang # 1 2 3, Qinyu Peng # 1 2, Xu Tian # 1 2, Cancan Chen 4, Xuanfeng Zhu 1 2, Changbai Huang 1 2, Zhiting Huo 1 2, Yang Liu 5, Chao Yang 6 7, Chao Liu 8 9, Ping Zhang 10 11
Journal Name Nat Commun
Pubmed ID 38177122
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.
Used Model Huh7, A549, HeLa, 293T, Vero, BHK-21, C6/36
DOI 10.1038/s41467-023-44580-6