Abstract
Coxsackievirus A10 (CVA10) is an enterovirus that has caused global outbreaks of hand, foot, and mouth disease (HFMD), accompanied by neurological and systemic complications. Animal models that can simulate natural infections are necessary for studying viral pathogenesis. In this study, our objective was to establish a mouse-adapted strain (CVA10-P8) through serial passaging, which was capable of orally infecting 14-day-old ICR mice, leading to hind-limb paralysis and death. Viral titers in various tissues indicated tropism in muscle tissue, with significant increases observed in the brain, lung, and intestinal tissues as the infection progressed. Pathological examination revealed tissue damage in the muscles, brain, lungs, and intestines accompanied by neutrophil infiltration of the brain. Furthermore, flow cytometry and transcriptome analysis revealed metabolic abnormalities, immune system activation, and the promotion of systemic inflammatory responses in the brain, muscle, and lung tissues. In summary, we successfully developed a CVA10 mouse-adapted strain and a corresponding mouse model, providing valuable tools for studying CVA10 pathogenesis and evaluating the efficacy of antiviral interventions.IMPORTANCECVA10 has emerged as a predominant pathogen in the etiology of HFMD, with the potential to elicit neurological manifestations and systemic complications. In this study, we successfully established a novel murine model of CVA10 infection by serially propagating a clinical isolate of CVA10, which enabled oral infection in 14-day-old ICR mice. This model facilitated the investigation of the pathogenesis of CVA10-induced disease. Utilizing this infection model, we employed flow cytometry and transcriptome analysis to elucidate the central nervous system (CNS) inflammatory responses elicited by CVA10 in mice, which closely mimic the natural route of infection. Our findings provide novel insights into the pathophysiological mechanisms underlying CVA10-induced neuroinflammation and pave the way for further research into targeted therapeutic interventions for HFMD associated with CVA10.