SFTSV NSs sequesters the complex of SFTSV NP-SAFA to suppress SAFA mediated immune response.

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 cytoplasmic RNA sensor, recognizes SFTSV infection and facilitates antiviral immune response.

Intriguingly, we discovered that SFTSV NSs triggers nucleocytoplasmic translocation of SAFA. Nevertheless, whether the interaction between SAFA and NSs mediates the suppression of host innate immunity remains unresolved. Herein, we demonstrate that after SFTSV infection, SAFA retains in cytoplasm by interacting with NP, meanwhile, NSs captures NP- SAFA complex into inclusion bodies (IBs) through direct interaction with SPRY, AAA+ and RGG domains of SAFA, without affecting its expression levels.