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Virus Details


VHFID3424

Host Factor Information

Pathogen Information

Publication Information

Host Factor Information

Gene Name TNK2
HF Protein Name Activated CDC42 kinase 1
HF Function Involved in Hepatitis C Virus entry
Uniprot ID Q07912
Protein Sequence View Fasta Sequence
NCBI Gene ID 10188
Host Factor (HF) Name in Paper TNK2
Gene synonyms ACK1
Ensemble Gene ID ENSG00000061938
Ensemble Transcript ENST00000333602 [Q07912-1];ENST00000381916 [Q07912-3];ENST00000439230 [Q07912-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0004674, GO:0004712, GO:0004713, GO:0004715, GO:0005095, GO:0005154, GO:0005524, GO:0005634, GO:0005737, GO:0005768, GO:0005886, GO:0005905, GO:0005912, GO:0006897, GO:0007166, GO:0007169, GO:0007264, GO:0016020, GO:0016310, GO:0016477, GO:0030136, GO:0030154, GO:0030659, GO:0031234, GO:0031625, GO:0038083, GO:0042127, GO:0042802, GO:0045087, GO:0046872, GO:0048471, GO:0050699, GO:0050731, GO:0070436, GO:2000369,
MINT ID Q07912
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 606994
PANTHER ID PTHR14254:SF4
PDB ID(s) 1CF4, 1U46, 1U4D, 1U54, 3EQP, 3EQR, 4EWH, 4HZR, 4HZS, 4ID7,
pfam ID PF09027, PF11555, PF07714, PF14604,
Drug Bank ID DB00171, DB04367,
ChEMBL ID CHEMBL4599
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Hepatitis C virus
Virus Short Name HCV
Order Unassigned
Virus Family Flaviviridae
Virus Subfamily N.A.
Genus Hepacivirus
Species Hepatitis C virus
Host Human
Cell Tropism Hepatocytes
Associated Disease Hepatitis, hepatocellular carcinoma
Mode of Transmission Sexual contact, blood
VIPR DB link http://www.viprbrc.org/brc/home.spg?decorator=flavi
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae
Virus Host DB link http://www.genome.jp/virushostdb/view/?virus_lineage=Flaviviridae

Publication Information

Paper Title EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy
Author's Name Joachim Lupberger, Mirjam B Zeisel, Fei Xiao, Christine Thumann, Isabel Fofana, Laetitia Zona, Christopher Davis, Christopher J Mee, Marine Turek, Sebastian Gorke, Cathy Royer, Benoit Fischer, Muhammad N Zahid, Dimitri Lavillette, Judith Fresquet, François-Lolc Cosset, S Michael Rothenberg, Thomas Pietschmann, Arvind H Patel, Patrick Pessaux, Michel Doffoël, Wolfgang Raffelsberger, Olivier Poch, Jane A McKeating, Laurent Brino & Thomas F Baumert
Journal Name Nature Medicine
Pubmed ID 21516087
Abstract Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.
Used Model Huh7.5.1 cells
DOI 10.1038/nm.2341