Flavivirus-NS1 triggers the Type-I interferon response through miR-145-5p mediated regulation of scavenger receptor class B1 in human cerebral microvascular endothelial cells.

Flavivirus non-structural protein 1 (NS1) is a highly conserved secreted protein that plays a crucial role in host-virus interaction during virus pathogenesis. Flavivirus-NS1 modulates the host's cellular and immunological responses. We explored miR-145-5p mediated expression of type I interferon (IFN) in flavivirus-NS1 triggered human cerebral microvascular endothelial cells (hCMEC/D3 cells) through scavenger receptor class B 1 (SR-B1). SR-B1 is an important lipoprotein receptor involved in cholesterol transport and lipid homeostasis. The increased expression of miR-145-5p in flavivirus-NS1 exposed hCMEC/D3 cells was reported using TaqMan-based quantitative PCR assay. The miR-145-5p mediated regulation of SR-B1 was validated by overexpression and knockdown of miR-145-5p in hCMEC/D3 cells. The increased expression of miR-145-5p led to the suppressed expression of SR-B1, which induced the expression of type I IFN - α/β. The protein expression patterns of SR-B1 and IFN- α/β were studied by immunoblotting. This study demonstrates miR-145-5p mediated type I IFN signaling by suppressing the SR-B1 expression through bystander effects of flavivirus-NS1 in human cerebral microvascular endothelial cells.