VLDLR mediates Semliki Forest virus neuroinvasion through the blood-cerebrospinal fluid barrier
Year: 2024
Type: article
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. 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.
Source: Nature Communications
Authors: Miika Martikainen, Roberta Lugano, Ilkka Pietilä, Sofie Brosch, Camille Cabrolier, Aishwarya Sivaramakrishnan, Mohanraj Ramachandran, Di Yu, Anna Dimberg, Magnus Essand
Institutions: Uppsala University, Science for Life Laboratory
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: G2488392785, G3359715895, Boosting CAR-T cells for improved cancer immunotherapy, Utveckling av CAR T celler för behandling av hjärntumörer hos barn, G6265702644, G6706913234, Cancer immunotherapy using next generation oncolytic viruses and CAR T cells, G7328747571, G7569742080, CAR-T celler med förmåga att inducera immunitet i hjärntumörer hos barn, G816265424, NAISS
OpenAlex ID: W4405701734