Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections

Takuma Ariizumi1, Koshiro Tabata2, Yukari Itakura2

  • 1Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.

Plos Pathogens
|March 19, 2024
PubMed

Insights

A new mouse model using AG129 mice effectively mimics Yezo virus (YEZV) infection, aiding research into tick-borne orthonairoviruses and testing antiviral drugs like favipiravir.

Area of Science:

  • Virology
  • Pathogenesis
  • Infectious Diseases

Background:

  • Emerging tick-borne orthonairoviruses, distinct from Crimean-Congo hemorrhagic fever virus, are increasingly reported in East Asia.
  • Yezo virus (YEZV) is a novel orthonairovirus causing febrile illness after tick bites in Japan and China.

Purpose of the Study:

  • To establish a mouse model for studying YEZV pathogenesis and evaluating antiviral therapies.
  • To better understand emerging tick-borne orthonairovirus infections.

Main Methods:

  • Utilized type-I/II interferon receptor-knockout (AG129) mice for YEZV infection studies.
  • Monitored disease progression, including weight loss and mortality.
  • Assessed liver damage via blood biochemistry.
  • Evaluated favipiravir efficacy in YEZV-infected mice.

Main Results:

  • YEZV-inoculated AG129 mice exhibited hepatitis, weight loss, and succumbed within 6 days.
  • Elevated liver enzymes in mice mirrored findings in human YEZV patients.
  • Favipiravir treatment conferred survival against lethal YEZV challenge.

Conclusions:

  • The AG129 mouse model accurately reflects YEZV-induced hepatitis and serves as a valuable tool for pathogenesis research.
  • This model facilitates the validation of antiviral agents against emerging tick-borne orthonairoviruses.