2. Academic Validation
  3. A mouse-adapted Yezo virus model for antiviral testing in immunocompetent mice

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

  • Nat Commun. 2026 Mar 17;17(1):4058. doi: 10.1038/s41467-026-70851-z.
Wenbo Xu # 1 2,  Yuanzhi Wang # 3,  Mingming Pan 1,  Qianqian Tan 1,  Fangyu Jin 1,  Liyan Sui 1,  Yinghua Zhao 1,  Nan Liu 4,  Quan Liu 5 6
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
  • 2 Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China.
  • 3 Department of Pathogenic Biology, School of Medicine, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region, Shihezi, Xinjiang, China.
  • 4 Department of Infectious Diseases and Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, The First Hospital of Jilin University, Changchun, China. [email protected].
  • 5 Department of Infectious Diseases and Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, The First Hospital of Jilin University, Changchun, China. [email protected].
  • 6 Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China. [email protected].
  • # Contributed equally.
PMID: 41844638 DOI: 10.1038/s41467-026-70851-z
Abstract

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.

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