| Gene Name | ZC3HAV1 |
| HF Protein Name | Zinc finger CCCH-type antiviral protein 1 |
| HF Function | Inhibits Hepatitis B Virus replication |
| Uniprot ID | Q7Z2W4 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 56829 |
| Host Factor (HF) Name in Paper | ZAP |
| Gene synonyms | ZC3HDC2 |
| Ensemble Gene ID | ENSG00000105939 |
| Ensemble Transcript | ENST00000242351 [Q7Z2W4-1];ENST00000471652 [Q7Z2W4-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0003723, GO:0005634, GO:0005737, GO:0005829, GO:0009615, GO:0032727, GO:0032728, GO:0043123, GO:0045071, GO:0045087, GO:0045296, GO:0046872, GO:0051607, GO:0061014, GO:1900246, |
| MINT ID | Q7Z2W4 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 607312 |
| PANTHER ID | N.A. |
| PDB ID(s) | 2X5Y, 4X52, |
| pfam ID | PF00644, PF02825, |
| 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 Replication by the Host Zinc Finger Antiviral Protein |
| Author's Name | Richeng Mao, Hui Nie, Dawei Cai, Jiming Zhang, Hongyan Liu, Ran Yan, Andrea Cuconati, Timothy M. Block, Ju-Tao Guo, Haitao Guo |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 23853601 |
| Abstract | The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor that inhibits the replication of a variety of RNA viruses, including retroviruses, alphaviruses and filoviruses, through interaction with the ZAP-responsive elements (ZRE) in viral RNA, and recruiting the exosome to degrade RNA substrate. Hepatitis B virus (HBV) is a pararetrovirus that replicates its genomic DNA via reverse transcription of a viral pregenomic (pg) RNA precursor. Here, we demonstrate that the two isoforms of human ZAP (hZAP-L and -S) inhibit HBV replication in human hepatocyte-derived cells through posttranscriptional down-regulation of viral pgRNA. Mechanistically, the zinc finger motif-containing N-terminus of hZAP is responsible for the reduction of HBV RNA, and the integrity of the four zinc finger motifs is essential for ZAP to bind to HBV RNA and fulfill its antiviral function. The ZRE sequences conferring the susceptibility of viral RNA to ZAP-mediated RNA decay were mapped to the terminal redundant region (nt 1820-1918) of HBV pgRNA. In agreement with its role as a host restriction factor and as an innate immune mediator for HBV infection, ZAP was upregulated in cultured primary human hepatocytes and hepatocyte-derived cells upon IFN-α treatment or IPS-1 activation, and in the livers of hepatitis B patients during immune active phase. Knock down of ZAP expression increased the level of HBV RNA and partially attenuated the antiviral effect elicited by IPS-1 in cell cultures. In summary, we demonstrated that ZAP is an intrinsic host antiviral factor with activity against HBV through down-regulation of viral RNA, and that ZAP plays a role in the innate control of HBV replication. Our findings thus shed light on virus-host interaction, viral pathogenesis, and antiviral approaches. |
| Used Model | HepG2, Huh7 and 293T cells |
| DOI | 10.1371/journal.ppat.1003494 |
