Virus Details


VHFID10021

Host Factor Information

Gene Name NCL
HF Protein Name Nucleolin
HF Function
Uniprot ID P19338
Protein Sequence View Fasta Sequence
NCBI Gene ID 4691
Host Factor (HF) Name in Paper NCL
Gene synonyms N.A.
Ensemble Gene ID ENSG00000115053
Ensemble Transcript ENST00000322723.9
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0001525, GO:0001533, GO:0003723, GO:0005634, GO:0005654, GO:0005681, GO:0005694, GO:0005730, GO:0005886, GO:0005938, GO:0016020, GO:0017148, GO:0036464, GO:0042162, GO:0042731, GO:0042802, GO:0043560, GO:0044547, GO:0045944, GO:0046627, GO:0048026, GO:0048027, GO:0070062, GO:0071364, GO:0160056, GO:1901838, GO:1990830, GO:1990904,
MINT ID P19338
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 164035
PANTHER ID PTHR23236;PTHR23236:SF119
PDB ID(s) 2FC8, 2FC9, 2KRR,
pfam ID PF00076,
Drug Bank ID N.A.,
ChEMBL ID CHEMBL4295725
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 Japanese encephalitis virus NS5 protein interacts with nucleolin to enhance the virus replication
Author's Name Arundhati Deb , Shilpi Nagpal, Rajnesh Kumari Yadav, Harsh Thakur, Deepak Nair, Vengadesan Krishnan, Sudhanshu Vrati
Journal Name Journal Of Virology
Pubmed ID 39078257
Abstract Japanese encephalitis virus (JEV) is an arthropod-borne, plus-strand flavivirus causing viral encephalitis in humans with a high case fatality rate. The JEV non-structural protein 5 (NS5) with the RNA-dependent RNA polymerase activity interacts with the viral and host proteins to constitute the replication complex. We have identified the multifunctional protein Nucleolin (NCL) as one of the several NS5-interacting host proteins. We demonstrate the interaction and colocalization of JEV NS5 with NCL in the virus-infected HeLa cells. The siRNA-mediated knockdown of NCL indicated that it was required for efficient viral replication. Importantly, JEV grew to higher titers in cells over-expressing exogenous NCL, demonstrating its pro-viral role. We demonstrated that NS5 interacted with the RRM and GAR domains of NCL. We show that the NCL-binding aptamer AS1411 containing the G-quadruplex (GQ) structure and the GQ ligand BRACO-19 caused significant inhibition of JEV replication. The antiviral effect of AS1411 and BRACO-19 could be overcome in HeLa cells by the overexpression of exogenous NCL. We demonstrated that the synthetic RNAs derived from the 3′-NCR of JEV genomic RNA containing the GQ sequence could bind NCL in vitro. The replication complex binding to the 3′-NCR is required for the viral RNA synthesis. It is likely that NCL present in the replication complex destabilizes the GQ structures in the genomic RNA, thus facilitating the movement of the replication complex resulting in efficient virus replication.
Used Model Neuro-2a (N2a), HeLa, Vero, C6/36, HAP1
DOI 10.1128/jvi.00858-24