Structural insights into VLDLR recognition by western equine encephalitis virus.

ABSTRACT: Western equine encephalitis virus (WEEV), a group of encephalitic alphaviruses that cause severe diseases in humans and equids, historically used the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection. However, current epidemic strains no longer use VLDLR as a receptor. In this study, we identify that LA1, LA2, LA3, and LA5 of VLDLR can directly interact with WEEV. Using cryo-electron microscopy, we investigate the structures of complexes formed between WEEV and VLDLR-LBD or other VLDLR fragments. Our findings show that LA1 and LA2 insert into a cleft formed by two adjacent E2-E1 heterodimers within a single trimeric spike, while LA3 and LA5 interact with the DIII region of WEEV E1. Among VLDLR concatemers, the LA1-5 exhibits the strongest binding affinity for WEE

SUBMITTER: Liang S 

PROVIDER: S-EPMC12800238 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature