Figure 2.

Mechanisms of SFTSV immune evasion. Regulatory mechanisms of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) on innate immune recognition, interferon production, and downstream antiviral effector pathways following host cell infection. Under conditions of mitochondrial damage or infection-induced stress, mitochondrial DNA (mtDNA) is released into the cytoplasm and recognized by cGAS, activating the STING-TBK1-IRF3 signaling axis to induce the expression of type I interferons (IFNs) and related antiviral genes. Concurrently, the RIG-I-MAVSTBK1/ IKK-IRF7 pathway is involved in viral RNA recognition and the activation of consecutive immune responses. SFTSV proteins intervene in host antiviral responses via multiple cellular targets. NP interacts with host factors such as A2B1 and SAFA to suppress cGAS-STING signaling and promote viral ribonucleoprotein (RNP) replication. Additionally, the virus modulates the WNTDVL- CTNNB1 pathway to influence host transcriptional responses. On the other hand, NSs induces the formation of inclusion bodies (IBs) to suppress host immune responses, and impacts autophagy as well as RNA interference (RNAi) processes by regulating molecules such as vimentin, Beclin1, and AGO2. Meanwhile, the virus interferes with PRR-IFN-JAK-STAT signal transduction, suppressing the expression of antiviral effector genes such as MxA, IFITM3, and NF-κB. Overall, SFTSV achieves robust immune evasion and facilitates viral replication and release by dampening pathogen recognition, intercepting interferon signaling, and remodeling intracellular homeostasis.