Disruption of Type I Interferon Signaling by the Nonstructural Protein of Severe Fever with Thrombocytopenia Syndrome Virus via the Hijacking of STAT2 and STAT1 into Inclusion Bodies

Abstract

SFTSV is an emerging bunyavirus which can cause a severe hemorrhagic fever-like disease with high case fatality rates in humans, posing a serious health threat. However, there are no specific antivirals available, and the pathogenesis and virus-host interactions are largely unclear. Here, we demonstrated that SFTSV can inhibit type I IFN antiviral signaling by the NSs-mediated hijacking of STAT2 and STAT1 into viral IBs, highlighting the interesting role of viral IBs in virus-host interactions as the virus-built jail. Sequestering signaling molecules into IBs represents a novel and, perhaps, also a general mechanism of viral suppression of IFN signaling, the understanding of which may benefit the study of viral pathogenesis and the development of antiviral therapies.