Emerging tick-borne viral diseases in East Asia: pathology-driven insights into pathogenesis and disease causality.
SUMMARYTick-borne viral infections have emerged as a significant and growing public health concern. In East Asia, severe fever with thrombocytopenia syndrome (SFTS) has served as a prototypical disease in which pathological analyses have substantially advanced the understanding of disease pathogenesis. SFTS is characterized by profound immune dysregulation driven by viral tropism for plasmablast-lineage B cells, leading to cytokine storm and hemophagocytic syndrome. Complementary analyses of human clinical specimens and experimental animal models, including cats and ferrets, have provided critical insights into the immunopathogenesis of SFTS. The recent identification of additional tick-borne viruses, including Oz virus (OZV), Yezo virus (YEZV), and Alongshan virus (ALSV), has further expanded the spectrum of emerging infections in this region. Notably, pathological investigation of a fatal human case of OZV infection demonstrated direct viral localization within cardiomyocytes, establishing a causal link between infection and fulminant myocarditis and highlighting a distinct organ-specific pathogenic mechanism. Despite the advances in genomic technologies that enable rapid detection of novel viruses, establishing causal relationships between viral presence and disease remains a major challenge. Tissue-based pathological approaches, particularly in situ localization of viral components, are, therefore, essential for defining disease mechanisms and confirming etiological roles. This review provides a comprehensive synthesis of tick-borne viral infections in East Asia, with particular emphasis on Japan, integrating pathological, virological, and clinical perspectives. It also identifies key knowledge gaps and underscores the importance of a synergistic One Health framework that incorporates both human and veterinary pathology to advance the understanding and control of these emerging diseases.