Gene Name | ONECUT1 |
HF Protein Name | Hepatocyte nuclear factor 6 |
HF Function | Inhibits virus gene expression and replication |
Uniprot ID | Q9UBC0 |
Protein Sequence | View Fasta Sequence |
NCBI Gene ID | 3175 |
Host Factor (HF) Name in Paper | HNF6 |
Gene synonyms | HNF6 HNF6A |
Ensemble Gene ID | ENSG00000169856 |
Ensemble Transcript | ENST00000305901 |
KEGG ID | Go to KEGG Database |
Gene Ontology ID(s) | GO:0000981, GO:0001077, GO:0001889, GO:0001952, GO:0002064, GO:0003677, GO:0005634, GO:0006006, GO:0006355, GO:0007219, GO:0007492, GO:0009653, GO:0030154, GO:0030183, GO:0030335, GO:0030512, GO:0031018, GO:0045165, GO:0045944, GO:0048536, GO:0048731, GO:0060271, |
MINT ID | N.A. |
STRING | Click to see interaction map |
GWAS Analysis | Click to see gwas analysis |
OMIM ID | 604164 |
PANTHER ID | N.A. |
PDB ID(s) | N.A., |
pfam ID | PF02376, PF00046, |
Drug Bank ID | N.A., |
ChEMBL ID | N.A. |
Organism | Homo sapiens (Human) |
Virus Name | Hepatitis B virus |
Virus Short Name | HBV |
Order | Unassigned |
Virus Family | Hepadnaviridae |
Virus Subfamily | N.A. |
Genus | Orthohepadnavirus |
Species | Hepatitis B virus |
Host | Human, mammals |
Cell Tropism | Hepatocytes |
Associated Disease | Hepatitis, hepatocellular carcinoma(chronic infections), cirrhosis |
Mode of Transmission | Sexual contact, blood, maternal-neonatal |
VIPR DB link | N.A. |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/reverse-transcribing-dna-and-rna-viruses-2011/w/rt_viruses/155/hepadnaviridae |
Virus Host DB link | N.A. |
Paper Title | Inhibition of Hepatitis B Virus Gene Expression and Replication by Hepatocyte Nuclear Factor 6 |
Author's Name | Ruidong Hao, Jing He, Xing Liu, Guozhen Gao, Dan Liu, Lei Cui, Guojun Yu, Wenhui Yu, Yu Chen, Deyin Guo |
Journal Name | Journal Of Virology |
Pubmed ID | 25653429 |
Abstract | Hepatitis B virus (HBV), a small enveloped DNA virus, chronically infects more than 350 million people worldwide and causes liver diseases from hepatitis to cirrhosis and liver cancer. Here, we report that hepatocyte nuclear factor 6 (HNF6), a liver-enriched transcription factor, can inhibit HBV gene expression and DNA replication. Overexpression of HNF6 inhibited, while knockdown of HNF6 expression enhanced, HBV gene expression and replication in hepatoma cells. Mechanistically, the SP2 promoter was inhibited by HNF6, which partly accounts for the inhibition on S mRNA. Detailed analysis showed that a cis element on the HBV genome (nucleotides [nt] 3009 to 3019) was responsible for the inhibition of the SP2 promoter by HNF6. Moreover, further analysis showed that HNF6 reduced viral pregenomic RNA (pgRNA) posttranscriptionally via accelerating the degradation of HBV pgRNA independent of La protein. Furthermore, by using truncated mutation experiments, we demonstrated that the N-terminal region of HNF6 was responsible for its inhibitory effects. Importantly, introduction of an HNF6 expression construct with the HBV genome into the mouse liver using hydrodynamic injection resulted in a significant reduction in viral gene expression and DNA replication. Overall, our data demonstrated that HNF6 is a novel host factor that can restrict HBV replication via both transcriptional and posttranscriptional mechanisms. |
Used Model | Huh-7.5 cells |
DOI | 10.1128/JVI.03094-14 |