| Gene Name | DNAJC14 |
| HF Protein Name | DnaJ homolog subfamily C member 14 |
| HF Function | Antiviral protein, modulates virus replication |
| Uniprot ID | Q6Y2X3 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 85406 |
| Host Factor (HF) Name in Paper | DNAJC14 |
| Gene synonyms | DRIP78 HDJ3 |
| Ensemble Gene ID | ENSG00000135392 |
| Ensemble Transcript | ENST00000317269;ENST00000317287;ENST00000357606 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0005789, GO:0015031, GO:0016020, GO:0016021, GO:0070062, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 606092 |
| PANTHER ID | N.A. |
| PDB ID(s) | N.A., |
| pfam ID | PF00226, PF14901, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Yellow fever virus |
| Virus Short Name | YFV |
| Order | Unassigned |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Yellow fever virus |
| Host | Human, mammals, mosquitoes and ticks |
| Cell Tropism | N.A. |
| Associated Disease | Hemorrhagic fever, encephalitis |
| Mode of Transmission | Arthropod bite, mainly mosquitoes |
| 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 |
| Paper Title | Identification and characterization of the host protein DNAJC14 as a broadly active flavivirus replication modulator |
| Author's Name | Zhigang Yi, Lindsey Sperzel, Cindy Nu ?rnberger, Peter J. Bredenbeek, Kirk J. Lubick, Sonja M. Best, Cristina T. Stoyanov, Lok Man J. Law, Zhenghong Yuan, Charles M. Rice, Margaret R. MacDonald |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 21249176 |
| Abstract | Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replicationcomplexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work, suggest that the members of the Flaviviridae family have evolved in unique and important ways to interact with this host Hsp40 chaperone molecule. |
| Used Model | HuH-7 cells and Vero cells |
| DOI | 10.1371/journal.ppat.1001255 |
