TBEV NS1 Induces Tissue-Specific Microvascular Endothelial Cell Permeability by Activation TNF-α Signaling Pathway

Background: /Objectives: Orthoflavivirus encephalitidis (tick-borne encephalitis virus, TBEV) is of high concern due to its ability to cause severe neurological manifestations. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis and their ability to affect human endothelial permeability was investi-gated, TBEV NS1 is insufficiently studied. Methods: Human endothelial permeability was assessed using PEER and transwell permeability assays. Signaling pathways were determined by RNAseq. Results: The ability of NS1 protein of TBEV to affect human endothelial permeability was investigated for the first time. It was shown that recombinant TBEV NS1 produced in eucaryotic cell directly affected on human lung microvascular endothelial cells (HLMVEC) in vitro but not on human umbilical vein endothelial cells (HUVEC). Conclusions: it was indicated that TBEV NS1 induced endothelial hyperpermeability of HLMVEC through activation TNF-α and other inflammatory signaling pathways.