SFTSV NSs Sequesters the Complex of SFTSV NP‐SAFA to Suppress SAFA Mediated Immune Response

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging pathogenic Bunyavirus with a fatality rate of up to 30%. SFTSV nonstructural protein (NSs) forms viroplasm-like structures in the cytoplasm of infected cells, sequestering antiviral proteins and inhibiting interferon signaling. Nuclear scaffold attachment factor A (SAFA), a novel RNA sensor, can be retained in the cytoplasm by SFTSV nucleoprotein (NP) and facilitates antiviral immune response. Intriguingly, we discovered that SFTSV NSs triggered the nucleocytoplasmic translocation of SAFA. Nevertheless, it remains unclear about the roles of NSs and NP in the recognition of SAFA and downstream signaling molecules. Herein, we demonstrate that after SFTSV infection, both of NP and NSs can interact with SPRY, AAA+ and RGG domains of SAFA in the cytoplasm. NSs can not only capture SAFA for degradation, but also sequester NP-SAFA complex into inclusion bodies (IBs), isolating and degrading SAFA with downstream signaling proteins. With the result that the nuclear translocation of p-IRF3 is prevented and the production of IFNβ is suppressed. In conclusion, our study reveals a novel immune evasion strategy for SFTSV by sequestering NP-SAFA complex to suppress IFNβ secretion.