Researchers identify how brain-invading viruses slip past immune defenses
Scientists have discovered that Semliki Forest virus breaks into the brain via a specific molecular doorway in the choroid plexus—not through the blood-brain barrier as previously assumed. The finding could reshape how companies develop treatments for viral brain infections and inform clinical strategies for blocking neurotropic viruses before they establish CNS infections.
Originaltitel: VLDLR mediates Semliki Forest virus neuroinvasion through the blood-cerebrospinal fluid barrier
<p>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. In laboratory mice, peripherally administered SFV infiltrates the central nervous system (CNS) and causes encephalitis of varying severity. The route of SFV CNS entrance is poorly understood but has been considered to occur through the blood-brain barrier. Here we show that neuroinvasion of intravenously administered SFV is strictly dependent on very-low-density-lipoprotein receptor (VLDLR) which acts as an entry receptor for SFV. Moreover, SFV primarily enters the CNS through the blood-cerebrospinal fluid (B-CSF) barrier via infecting choroid plexus epithelial cells which show distinctly high expression of VLDLR. This is the first indication of neurotropic alphavirus utilizing choroid plexus for CNS entry, and VLDLR playing a specific and crucial role for mediating SFV entry through this pathway.</p>