Studies On The Suppression Of Host Innate Immunity By Nonstructural Protein NSs Of Severe Fever With Thrombo- Cytopenia Syndrome Virus

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunya-virus, which has posed a serious health threat. SFTS disease is characterized by gas-trointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 12-30%. However, at present, little is known about the virus pathogenesis and virus-host inter-actions in humans infected with SFTSV. In this study, we examined host responses in the infected HEK293 cells and observed pro-inflammatory cytokines (IL-6 and IL-8) and antiviral IFNs (IFN-a and IFN-β) induction were suppressed. Furthermore, MAVS knockdown HEK293 cells allow up-regulated viral replication via decreased cytokines production but overexpression of MAVS in HEK293 cells can reverse this phenomenon. Using a combination of coimmunoprecipitation and confocal micros-copy, we found that SFTSV nonstructural protein NSs-formed viral inclusion bodies (IBs) colocalized with mitochondrial antiviral signaling protein MAVS, but not RIG-I or MDA-5, in infected and transfected-NSs HeLa cells or HEK293 cells. In conclu-sion, we found that SFTSV hijacked MAVS by sequestration it into viral inclusion bodies and inhibit IFNs and NF-κB responses. Our finding provides further evidence how SFTSV uses the novel mechanism to suppress host proinflammatory as well as antiviral responses.