| Gene Name | GDF15 |
| HF Protein Name | Growth/differentiation factor 15 |
| HF Function | Promotes Human Rhinovirus Infection |
| Uniprot ID | Q99988 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 9518 |
| Host Factor (HF) Name in Paper | GDF15 |
| Gene synonyms | MIC1 PDF PLAB PTGFB |
| Ensemble Gene ID | ENSG00000130513 |
| Ensemble Transcript | ENST00000252809 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0005125, GO:0005160, GO:0005576, GO:0005615, GO:0005634, GO:0005737, GO:0005794, GO:0007165, GO:0007179, GO:0007267, GO:0008083, GO:0010862, GO:0030509, GO:0042981, GO:0043408, GO:0048468, GO:0060395, GO:0070062, GO:1901741, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 605312 |
| PANTHER ID | PTHR11848 |
| PDB ID(s) | 5VT2, 5VZ3, 5VZ4, |
| pfam ID | PF00019, |
| Drug Bank ID | N.A., |
| ChEMBL ID | CHEMBL3120039 |
| Organism | Homo sapiens (Human) |
| Virus Name | Human rhinovirus A |
| Virus Short Name | HRV-A1 |
| Order | Picornavirales |
| Virus Family | Picornaviridae |
| Virus Subfamily | N.A. |
| Genus | Enterovirus |
| Species | Rhinovirus A |
| Host | Human, mammals |
| Cell Tropism | Upper respiratory tract |
| Associated Disease | Common cold |
| Mode of Transmission | Either fecal-oral or respiratory |
| VIPR DB link | https://www.viprbrc.org/brc/home.spg?decorator=picorna |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/234/picornaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Picornaviridae |
| Paper Title | Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung |
| Author's Name | Qun Wu, Di Jiang, Niccolette R. Schaefer, Laura Harmacek, Brian P. OConnor, Thomas E. Eling, Oliver Eickelberg, and Hong Wei Chu |
| Journal Name | American Journal of Physiology-Lung Cellular and Molecular Physiology |
| Pubmed ID | 29192094 |
| Abstract | Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. We first examined the role of GDF15 in regulating host defense and HRV-induced inflammation using human GDF15 transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial cells. Next, we determined the effect of GDF15 on viral replication, antiviral responses, and inflammation in human airway epithelial cells with GDF15 knockdown and HRV infection. Finally, we explored the signaling pathways involved in airway epithelial responses to HRV infection in the context of GDF15. Human GDF15 protein overexpression in mice led to exaggerated inflammatory responses to HRV, increased infectious particle release, and decreased IFN-lambda2/3 (IL-28A/B) mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and inflammation via inhibiting IFN-lambda1/IL-29 protein production in human airway epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7 (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15 signaling. Our results reveal a novel function of GDF15 in promoting lung HRV infection and virus-induced inflammation, which may be a new mechanism for the increased susceptibility and severity of respiratory viral (i.e., HRV) infection in cigarette smoke-exposed airways with GDF15 overproduction. |
| Used Model | Human GDF15 transgenic (hGDF15 Tg plus) mouse |
| DOI | 10.1152/ajplung.00324.2017 |
