SFTSV utilizes AXL/GAS6 for entry via PI3K-PLC-dependent macropinocytosis activated by AXL-kinase.

ABSTRACT: Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern caused by SFTS virus (SFTSV), a tick-borne RNA virus. Previous studies have identified DC-SIGN and related C-type lectins as receptors of SFTSV infection in specific cell populations. Our genome-wide CRISPR activation screening identified AXL, a receptor tyrosine kinase, as a novel entry receptor for SFTSV. We found that AXL-mediated SFTSV infection utilizes the bridging action of growth arrest-specific protein 6 between AXL and phosphatidylserine on virus particles. This interaction induces autophosphorylation of tyrosine residues in the intracellular domain of AXL, recruiting phosphatidylinositol-3 kinase (PI3K) and phospholipase C (PLC) and establishing a macropinocytotic pathway of SFTSV entry. Th

SUBMITTER: Jin Z 

PROVIDER: S-EPMC12455926 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature