A mouse-adapted CVA6 strain successfully infected 10-day-old ICR mice via the oral route, resulting in 100% mortality, paralysis, and systemic manifestations including neurotropism and multi-organ damage.
A novel mouse-adapted CVA6 strain successfully models the neurological and systemic complications of HFMD in 10-day-old ICR mice, providing a useful tool for evaluating antivirals and vaccines.
Absolute Event Rate: 100% vs 0%
CVA6 is one of Enteroviruses causing worldwide epidemics of HFMD with neurological and systemic complications. A suitable animal model is necessary for studying the pathogenesis of CVA6 and evaluating antiviral and vaccine efficacy. In this study, we generated a mouse-adapted CVA6 strain that successfully infected 10-day-old ICR mice via oral route. All infected mice were paralyzed and died within 11 dpi. Analysis of pathological changes and virus loads in fourteen tissues showed that CVA6 triggered systematic damage similar to i.p. inoculation route. Unlike i.p. route, we detected oral and gastrointestinal lesions with the presence of viral antigens. Both specific anti-CVA6 serum and inactivated vaccines successfully generated immune protection in mice. Meanwhile, we also established a successful infection of CVA6 via i.p. and i.m. route in 10-day-old mice. After infection, mice developed remarkably neurological signs and systemic manifestations such as emaciation, polypnea, quadriplegia, depilation and even death. Through i.p. inoculation, pathological examination showed brain and spinal cord damage caused by the virus infection with neuronal reduction, apoptosis, astrocyte activation, and recruitment of neutrophils and monocytes. Following neurological manifestation, the CVA6 infection became systemic, and high viral loads were detected in multiple organs along with morphological changes and inflammation. Moreover, analysis of spleen cells by FACS indicated that CVA6 led to immune system activation, which further contributed to systemic inflammation. Taken together, our novel murine model of CVA6 provides a useful tool for studying the pathogenesis and evaluating antiviral and vaccine efficacy.
Li et al. (Sat,) conducted a other in CVA6 infection. Mouse-adapted CVA6 strain vs. Mock infection was evaluated on Mortality. A mouse-adapted CVA6 strain successfully infected 10-day-old ICR mice via the oral route, resulting in 100% mortality, paralysis, and systemic manifestations including neurotropism and multi-organ damage.