Pathogenicity of a novel orthonairovirus, Iwanai Valley virus, in mice.

Iwanai Valley virus (IWVV) is a novel tick-borne orthonairovirus classified into the Tamdy genogroup. Since several orthonairoviruses in the Tamdy and closely related Sulina genogroups have been associated with human diseases, evaluating the pathogenic potential of IWVV is an important public health priority. Despite the increase in reports of orthonairoviruses belonging to the Tamdy and Sulina genogroups in East Asia, studies on their pathogenicity remain limited. In this study, we established a mouse model of IWVV infection using type I interferon receptor knockout (IFNAR1-/-) mice and analyzed the pathogenicity of IWVV infection. IWVV infection was lethal in IFNAR1-/-mice but did not cause any significant symptoms in BALB/c mice. IWVV replicated well in the liver and spleen of IFNAR1-/-mice, leading to acute necrotizing hepatitis and damage to the spleen, characterized by lymphocyte depletion. These pathological features are consistent with those observed in immunocompromised mice infected with other human-pathogenic orthonairoviruses, such as Crimean-Congo hemorrhagic fever virus and Yezo virus. Although human infections with IWVV have not been reported, the observed virulence in animal models suggests that further evaluation of its zoonotic potential is warranted. Our findings highlight the importance of continued surveillance of emerging tick-borne IWVV to assess potential risks to public health.