Vldlr, the very-low-density lipoprotein receptor, is involved in multiple biological processes. It has been implicated in lipid metabolism, as endoplasmic reticulum (ER) stress-mediated increases in hepatic Vldlr levels promote hepatic steatosis by enhancing the delivery of triglyceride-rich lipoproteins to the liver [4]. Additionally, it plays a role in alphavirus infection, as it serves as a receptor for multiple alphaviruses such as Semliki forest virus, eastern equine encephalitis virus, and Western equine encephalitis virus [1,2,3].

In in vivo studies, Vldlr-deficient mice show markedly diminished pathogenicity of WEEV, EEEV, and SFV, indicating that Vldlr is required for the pathogenesis of these encephalitic alphaviruses [3]. Also, neuroinvasion of intravenously administered SFV is strictly dependent on Vldlr, which acts as an entry receptor for SFV and mediates its entry through the blood-cerebrospinal fluid barrier [5].

In conclusion, Vldlr is essential in both lipid-related physiological processes and viral pathogenesis. The use of Vldlr-deficient mouse models has significantly enhanced our understanding of its role in alphavirus-induced encephalitis, providing potential avenues for developing countermeasures against these viruses.