Scholarlink

<p>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 WEEV. Additionally, we find that a single polymorphism in the E2 glycoprotein determines WEEV’s receptor tropism. Mutations <sub>E2</sub>E181K or <sub>E2</sub>E81K in the nonpathogenic strain Imperial-181 enhanced its ability to enter via VLDLR. These results enhance our understanding of alphavirus receptor recognition and receptor usage shifts, providing insights for the development of antiviral therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structural insights into VLDLR recognition by western equine encephalitis virus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月6日

查看全文
  • Shengjian Liang,
  • Zhili Xu,
  • Xiaoke Liu,
  • Yan Yang,
  • Lixin Zhao,
  • Chuyu Hu,
  • Jichao Hou,
  • Zhenyu Wei,
  • Yan Zhang,
  • Donghan Li,
  • Jinwei Yang,
  • Jiayi Zhang,
  • Jundong Bi,
  • Yanyi Wang,
  • Zhiyong Lou

摘要

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 WEEV. Additionally, we find that a single polymorphism in the E2 glycoprotein determines WEEV’s receptor tropism. Mutations E2E181K or E2E81K in the nonpathogenic strain Imperial-181 enhanced its ability to enter via VLDLR. These results enhance our understanding of alphavirus receptor recognition and receptor usage shifts, providing insights for the development of antiviral therapies.