VLDLR mediates alphavirus neuroinvasion through the blood-cerebrospinal fluid barrier

Abstract Semliki Forest virus (SFV) is a neuropathogenic alphavirus which is of interest both as a model neurotropic alphavirus and as an oncolytic virus with proven potency in preclinical cancer models. The route of central nervous system (CNS) entrance of SFV is poorly understood but has been considered to occur through the blood-brain barrier. Here, we show that SFV primarily enters the CNS through the blood-cerebrospinal fluid barrier, and that VLDLR is crucial in enabling SFV infection of the choroid plexus epithelial cells.