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<p>Emerging tick-borne orthonairoviruses pose a growing public health threat, yet few animal models fully recapitulate human disease. Here, we report the development of a mouse-adapted Yezo virus (MA-YEZV) strain that causes lethal infection in immunocompetent mice, mirroring key clinical features of human infection, including thrombocytopenia, leukopenia, and severe liver injury. Serial passaging of YEZV in C57BL/6 J mice selected for 31 non-synonymous mutations, enhancing viral replication and pathogenicity. MA-YEZV exhibited broad tissue tropism, with the highest viral loads in the liver, and induced a robust inflammatory response marked by elevated proinflammatory cytokines (e.g., IFN-γ, TNF-α, IL-6) and inflammasome activation. Ribavirin treatment effectively suppressed viral replication, prevented mortality, and mitigated tissue damage, whereas remdesivir showed no efficacy. This model provides a critical tool for studying YEZV pathogenesis and antiviral development, while the identified mutations offer insights into viral adaptation and virulence mechanisms. Our findings underscore the potential of MA-YEZV as a platform for evaluating countermeasures against emerging orthonairoviruses.</p>

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A mouse-adapted Yezo virus model for antiviral testing in immunocompetent mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月17日

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  • Wenbo Xu,
  • Yuanzhi Wang,
  • Mingming Pan,
  • Qianqian Tan,
  • Fangyu Jin,
  • Liyan Sui,
  • Yinghua Zhao,
  • Nan Liu,
  • Quan Liu

摘要

Emerging tick-borne orthonairoviruses pose a growing public health threat, yet few animal models fully recapitulate human disease. Here, we report the development of a mouse-adapted Yezo virus (MA-YEZV) strain that causes lethal infection in immunocompetent mice, mirroring key clinical features of human infection, including thrombocytopenia, leukopenia, and severe liver injury. Serial passaging of YEZV in C57BL/6 J mice selected for 31 non-synonymous mutations, enhancing viral replication and pathogenicity. MA-YEZV exhibited broad tissue tropism, with the highest viral loads in the liver, and induced a robust inflammatory response marked by elevated proinflammatory cytokines (e.g., IFN-γ, TNF-α, IL-6) and inflammasome activation. Ribavirin treatment effectively suppressed viral replication, prevented mortality, and mitigated tissue damage, whereas remdesivir showed no efficacy. This model provides a critical tool for studying YEZV pathogenesis and antiviral development, while the identified mutations offer insights into viral adaptation and virulence mechanisms. Our findings underscore the potential of MA-YEZV as a platform for evaluating countermeasures against emerging orthonairoviruses.