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

• Published in: PLoS pathogens Vol. 20; no. 3; p. e1012101
• Main Authors: Ariizumi, Takuma, Tabata, Koshiro, Itakura, Yukari, Kobayashi, Hiroko, Hall, William W., Sasaki, Michihito, Sawa, Hirofumi, Matsuno, Keita, Orba, Yasuko
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2024; Public Library of Science (PLoS)
• Subjects: Analysis; Analysis and chemistry; Antigens; Antiviral agents; Antiviral drugs; Arachnids; Biochemistry; Biological response modifiers; Bites and stings; Blood; Body weight; Body weight loss; Care and treatment; Crimean hemorrhagic fever; Diagnosis; Dosage and administration; Enzymes; Fatalities; Females; Glucose; Health aspects; Hemorrhagic fever; Hepatitis; Infections; Insect bites; Interferon; Kinases; Leukopenia; Liver; Pathogenesis; Pathogenicity; Pathogens; Proteins; Risk factors; Spleen; Standard deviation; Thrombocytopenia; Tick-borne diseases; Viruses; Weight loss; Congo (Kinshasa); Japan; China; Ukraine
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012101

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.