SFTSV NSs protein is a novel tick antiviral RNAi response suppressor

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phenuivirus causing high mortality in humans. While the non-structural protein NSs is dispensable for replication in mammalian cells, we demonstrate for the first time that NSs is essential for viral replication in tick cells. SFTSV infection triggers canonical Dicer-2-mediated antiviral RNA interference (RNAi) in tick cells, producing virus-derived small interfering RNAs (siRNAs) that target viral transcripts for degradation. We show that NSs functions as a viral suppressor of RNAi by selectively sequestering single-stranded RNAs derived from 22-nucleotide siRNAs, preventing their incorporation into RNA-induced silencing complexes (RISC). Complementation with a heterologous RNAi suppressor (p19 protein) partially rescues replication of NSs-deficient virus, validating NSs’ RNAi suppressive function. These findings reveal that successful tick-borne viral replication requires host-specific immune evasion strategies and establish NSs-mediated RNAi suppression as essential for SFTSV persistence in arthropod vectors.