Scholarlink

<p>Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) which results in a high mortality rate and poses a public health threat. Gene variation of SFTSV is one of the major forces driving its persistence and widespread prevalence. However, how genetic variations affect virus invasion is not yet fully understood. In this study, we evaluated the adaptive advantage of three stable high-frequency substitutions D170N, I323V, and K619R located on the envelope glycoprotein of SFTSV based on 1041&#xa0;M segments of their genomes. The result demonstrated that single mutation of D170N, or K619R reduced infectivity of mutant. However, the combined presence of both D170N, and K619R mutation enhanced infectivity of mutants. Structure model and SPR assay studies indicated that the substitution at the 170 site reduced the binding affinity between Gn glycoprotein and host C-C motif chemokine receptor 2 (CCR2). Additionally, neutralization assay showed I323/K619R mutant exhibited completely resistance to neutralizing antibodies pressure. This study reveals that SFTSV balances its entry ability by gene variation of different loci on its glycoprotein via a trade-off between Gn and Gc. In addition, a weakened invasion strategy facilitated by site mutations benefits its immune evasion. The findings provide mechanistic insights into its prevalence, thereby enabling early warnings for potential future outbreaks.</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

Weakened invasion of severe fever with thrombocytopenia syndrome bunyavirus beneficial to its immune escape by multi-site mutation of glycoprotein

  • 期刊论文

  • 发表日期：

    2025年11月22日

查看全文
  • Lin Wang,
  • Jingjing Wang,
  • Juan Zhang,
  • Xin Wang,
  • Weiyou Cao,
  • Lilan Yang,
  • Yulong Wu,
  • Boqing Li,
  • Yuanyuan Qiao

摘要

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) which results in a high mortality rate and poses a public health threat. Gene variation of SFTSV is one of the major forces driving its persistence and widespread prevalence. However, how genetic variations affect virus invasion is not yet fully understood. In this study, we evaluated the adaptive advantage of three stable high-frequency substitutions D170N, I323V, and K619R located on the envelope glycoprotein of SFTSV based on 1041 M segments of their genomes. The result demonstrated that single mutation of D170N, or K619R reduced infectivity of mutant. However, the combined presence of both D170N, and K619R mutation enhanced infectivity of mutants. Structure model and SPR assay studies indicated that the substitution at the 170 site reduced the binding affinity between Gn glycoprotein and host C-C motif chemokine receptor 2 (CCR2). Additionally, neutralization assay showed I323/K619R mutant exhibited completely resistance to neutralizing antibodies pressure. This study reveals that SFTSV balances its entry ability by gene variation of different loci on its glycoprotein via a trade-off between Gn and Gc. In addition, a weakened invasion strategy facilitated by site mutations benefits its immune evasion. The findings provide mechanistic insights into its prevalence, thereby enabling early warnings for potential future outbreaks.