ZMPSTE24 defends against influenza and other pathogenic viruses

• DOI: 10.1084/jem.20161270
• Publication Date: 2017-02-28T15:14:02Z
• Authors: Bishi Fu; Lingyan Wang; Shitao Li; Martin E. Dorf
• Keywords: ISG15; Antiviral protein; Immunoprecipitation

Zinc metallopeptidase STE24 (ZMPSTE24) is a transmembrane metalloprotease whose catalytic activity critical for processing lamin A on the inner nuclear membrane and clearing clogged translocons endoplasmic reticulum. We now report ZMPSTE24 virus-specific effector that restricts enveloped RNA DNA viruses, including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, cowpox, vaccinia, but not murine leukemia or adenovirus. ZMPSTE24-mediated antiviral action independent of protease activity. Coimmunoprecipitation studies indicate can complex with proteins interferon-induced protein (IFITM) family. IFITM impede viral entry, expression necessary In vivo demonstrate ZMPSTE24-deficient mice display higher burdens, enhanced cytokine production, increased mortality after infection. Collectively, these findings identify as an intrinsic broad-spectrum provide insights into defense mechanisms.