Interplay between SFTSV and host innate immunity: Viral evasion mechanisms, pathogenesis, and therapeutic perspectives

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTSV, is an emerging tick-borne disease with substantial mortality in East Asia and increasing geographic reach. Here, we provide an updated conceptual framework that integrates classic host recognition via DNA and RNA sensors accompanied with the multifaceted immune evasion strategies orchestrated by the viral components. A central focus is that SFTSV utilizes host receptors for attachment and internalization while hijacking autophagy-related membranes to promote assembly and egress. Its NSs protein forms autophagic inclusion bodies that sequester and degrade innate immune factors, whereas NP and Gn interfere with RIG-I-MAVS and cGAS-STING signaling through autophagy-associated mechanisms. We also examine NS-driven inflammatory regulation and evidence that the microbiota shapes virus transmission and antiviral responses. Collectively, unraveling these intricate host-virus interactions will be pivotal for advancing targeted therapeutic strategies against SFTS.