| First Author | Fu B | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 4 | Pages | 919-929 |
| PubMed ID | 28246125 | Mgi Jnum | J:241516 |
| Mgi Id | MGI:5902878 | Doi | 10.1084/jem.20161270 |
| Citation | Fu B, et al. (2017) ZMPSTE24 defends against influenza and other pathogenic viruses. J Exp Med 214(4):919-929 |
| abstractText | Zinc metallopeptidase STE24 (ZMPSTE24) is a transmembrane metalloprotease whose catalytic activity is critical for processing lamin A on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum. We now report ZMPSTE24 is a virus-specific effector that restricts enveloped RNA and DNA viruses, including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, cowpox, and vaccinia, but not murine leukemia or adenovirus. ZMPSTE24-mediated antiviral action is independent of protease activity. Coimmunoprecipitation studies indicate ZMPSTE24 can complex with proteins of the interferon-induced transmembrane protein (IFITM) family. IFITM proteins impede viral entry, and ZMPSTE24 expression is necessary for IFITM antiviral activity. In vivo studies demonstrate ZMPSTE24-deficient mice display higher viral burdens, enhanced cytokine production, and increased mortality after influenza infection. Collectively, these findings identify ZMPSTE24 as an intrinsic broad-spectrum antiviral protein and provide insights into antiviral defense mechanisms. |
