The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages

SFTSV is a negative-strand RNA virus usually carried by the tick Haemaphysalis longicornis. HIDfsin2, the tick saliva peptide, activates the Toll-like receptor 4 (TLR4) by interacting with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles. And activating TLR4 enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4.This reaction enhances the antiviral innate immunity of mouse macrophages. Therefore, HIDfsin2 enhance SFTSV replication in A549 and Huh7 cells (human cell lines) with low expression of TLR4. On the other hands, HIDfsin2 suppress SFTSV replication in mouse peritoneal macrophages (MPMs) with high expression of TLR4.
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