Vldlr, the very-low-density lipoprotein receptor, is involved in the uptake of triglyceride-rich lipoproteins. It has been associated with hepatic steatosis, as endoplasmic reticulum (ER) stress-mediated increases in hepatic Vldlr levels promote this condition [3]. Additionally, it plays a role in the pathogenesis of multiple encephalitic alphaviruses [2].

In vivo studies using Vldlr-deficient mice have shown that the pathogenicity of Western equine encephalitis virus (WEEV), Eastern equine encephalitis virus (EEEV), and Semliki Forest virus (SFV) is markedly diminished [2]. A soluble Vldlr-Fc decoy molecule can protect mice against disease caused by these viruses, indicating Vldlr's crucial role in alphavirus pathogenesis [2]. Mice neonates can be protected from rapidly fatal SFV infection by the administration of a Vldlr LBD-Fc fusion protein, suggesting its potential as a countermeasure [1]. SFV's neuroinvasion into the central nervous system through the blood-cerebrospinal fluid barrier is strictly dependent on Vldlr [4].

In conclusion, Vldlr is important for lipoprotein uptake and has a significant role in the pathogenesis of multiple encephalitic alphaviruses. The use of Vldlr-deficient mouse models has provided valuable insights into its role in alphavirus-related diseases, which may contribute to the development of countermeasures against these viruses.

References:

1. Clark, Lars E, Clark, Sarah A, Lin, ChieYu, Weaver, Scott C, Abraham, Jonathan. 2021. VLDLR and ApoER2 are receptors for multiple alphaviruses. In Nature, 602, 475-480. doi:10.1038/s41586-021-04326-0. https://pubmed.ncbi.nlm.nih.gov/34929721/

2. Palakurty, Sathvik, Raju, Saravanan, Sariol, Alan, Klimstra, William B, Diamond, Michael S. 2024. The VLDLR entry receptor is required for the pathogenesis of multiple encephalitic alphaviruses. In Cell reports, 43, 114809. doi:10.1016/j.celrep.2024.114809. https://pubmed.ncbi.nlm.nih.gov/39369384/

3. Peyman, Mona, Babin-Ebell, Anna, Rodríguez-Rodríguez, Rosalía, Barroso, Emma, Vázquez-Carrera, Manuel. 2024. SIRT1 regulates hepatic vldlr levels. In Cell communication and signaling : CCS, 22, 297. doi:10.1186/s12964-024-01666-y. https://pubmed.ncbi.nlm.nih.gov/38807218/

4. Martikainen, Miika, Lugano, Roberta, Pietilä, Ilkka, Dimberg, Anna, Essand, Magnus. 2024. VLDLR mediates Semliki Forest virus neuroinvasion through the blood-cerebrospinal fluid barrier. In Nature communications, 15, 10718. doi:10.1038/s41467-024-55493-3. https://pubmed.ncbi.nlm.nih.gov/39715740/