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Feeding of Ticks on Animals for Transmission and Xenodiagnosis in Lyme Disease Research
Published on: August 31, 2013
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.
Abstract:
Emerging and reemerging tick-borne virus infections caused by orthonairoviruses (family Nairoviridae), which are genetically distinct from Crimean-Congo hemorrhagic fever virus, have been recently reported in East Asia. Here, we have established a mouse infection model using type-I/II interferon receptor-knockout mice (AG129 mice) both for a better understanding of the pathogenesis of these infections and validation of antiviral agents using Yezo virus (YEZV), a novel orthonairovirus causing febrile illnesses associated with tick bites in Japan and China. YEZV-inoculated AG129 mice developed hepatitis with body weight loss and died by 6 days post infection. Blood biochemistry tests showed elevated liver enzyme levels, similar to YEZV-infected human patients. AG129 mice treated with favipiravir survived lethal YEZV infection, demonstrating the anti-YEZV effect of this drug. The present mouse model will help us better understand the pathogenicity of the emerging tick-borne orthonairoviruses and the development of specific antiviral agents for their treatment.
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.

