Abstract:Objective To establish an animal model of hand, foot and mouth disease (HFMD) in Syrian hamsters coinfected with Coxsackievirus A6 (CVA6) and Coxsackievirus B1 (CVB1). Methods Twenty-four Syrian hamsters were divided into CVA6 infection group, CVB1 infection group, CVA6 and CVB1 coinfection group and control group. The model was established by nasal instillation of virus solution and PBS. Clinical indicators, physiological indicators, and detoxification status were monitored and recorded for 15 days, and animals were selected on D7 after infection for histopathology and viral antigen and nucleic acid testing. Results Hamsters in the single and coinfection groups showed clinical symptoms similar to human HFMD. The results of WBC, NEUT and LYMPH indicated the blood characteristics of viral infection. Both viral nucleic acids were detected in throat swabs, feces, blood and tissues. Both viruses were isolated in fecal samples. Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues. Conclusion The nasal instillation of CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters, replicate herpes similar to human hand, foot and mouth disease, and cause viral myocarditis and encephalitis pathological damage. The results showed that the coinfection group was more serious than the single infection group, with worse clinical symptoms, increased viral replication and obvious tissue pathological damage. This study provides a certain reference for the basic and clinical research of human enterovirus coinfection.