Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey.

Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity, ranging from mild to severe. However, traditional CVB3-infected mice studies have predominantly resulted in viral myocarditis and pancreatitis, failing to replicate HFMD symptoms. This has limited our understanding of CVB3 virus-host interaction. Meanwhile, the different clinical manifestations animal models could effectively accelerate the CVB3 novel therapies and vaccines development. Syrian hamsters and rhesus monkeys have been widely used to evaluate many enteroviruses, but CVB3 has not been reported systematically. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. Our research discovered that both intraperitoneal injection and nasal drip were effective for CVB3 to infect Syrian hamsters, resulting in characteristic HFMD symptoms, nasopharyngeal colonization, and acute severe pathological injury. Notably, the nasal drip group led to a longer detoxification cycle and more severe pathological damage. In the subsequent study, CVB3 infected rhesus monkeys through nasal drips also presented with HFMD symptoms, detoxification, serum antibody conversion, viral nucleic acids and antigens, and the specific organs pathological damage such as the heart. Surprisingly, no significant differences in myocardial enzyme levels were observed. And the clinical manifestations were akin to those of common, mild infections. In summary, the study established CVB3 severe Syrian hamster and mild rhesus monkey HFMD models, which laid a foundation for understanding the pathogenesis, pre-trial prevention and evaluation and post-exposure intervention.