biostudies-literatureAriizumi TMinistry of Health, Labour and WelfareMoonshot Research and Development ProgramJapan Agency for Medical Research and DevelopmentJapan Society for the Promotion of Sciencee1012101https://www.ebi.ac.uk/biostudies/studies/S-EPMC10980201biostudies-literatureUnknown20(3)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.PLoS pathogensEstablishment of a lethal mouse model of emerging tick-borne orthonairovirus infections.PMC10980201JP23fk0108644, JP23fk0108625, JP23jf0126002JP23H02373, JP23K20041JP21wm012500823HA2010223fa627005h0001JP22fk0108637JPMJMS2025Sawa HTabata KSasaki MMatsuno KAriizumi TOrba YKobayashi HItakura YHall WWfalseEstablishment of a lethal mouse model of emerging tick-borne orthonairovirus infections.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.2024-01-01T00:00:00Z2024 Mar2025-04-22T21:34:47.363Z2025-04-06T03:34:48.402ZS-EPMC109802013850264210.1371/journal.ppat.1012101