Crimean-Congo hemorrhagic fever virus NSm protein inhibits the type I interferon signaling by binding to STAT2.

The type I interferon (IFN-I) response, which includes IFN-I induction and signaling, plays an important role in a host's defence against viral infections. Many pathogenic viruses target it to evade the host immunity. Crimean-Congo hemorrhagic fever virus (CCHFV), the causative agent of Crimean-Congo hemorrhagic fever, which features high mortality in humans, has been reported in southeastern Europe, Africa, the Middle East, and Asia. Although a previous study reported that CCHFV antagonizes IFN-I signaling in human cell lines, it is unclear how it inhibits IFN-I signaling. Here we demonstrated that the non-structural protein of CCHFV, NSm, suppresses IFN-I signaling in human cell lines. Furthermore, we discovered that NSm binds to STAT2, an important host protein in IFN-I signaling, and induces its degradation within cells. Taken together, our results imply that NSm suppresses IFN-I signaling by targeting human STAT2.