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Published on: April 28, 2019
Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey
Suqin Duan1, Wei Zhang1, Yongjie Li1
1Institute of Medical Biology, Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease, Kunming, 650118, China.
Abstract:
Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention.
Insights
New animal models for hand, foot, and mouth disease (HFMD) caused by Coxsackievirus B3 (CVB3) were developed. Syrian hamsters showed severe HFMD symptoms, while rhesus monkeys exhibited milder infections, aiding disease research.
Area of Science:
- Virology and Infectious Diseases
- Animal Models of Human Disease
Background:
- Coxsackievirus B3 (CVB3) causes hand, foot, and mouth disease (HFMD) with variable clinical severity.
- Existing mouse models do not accurately replicate human HFMD symptoms, showing primarily myocarditis and pancreatitis.
- Limited data exists on CVB3 infection in Syrian hamsters and rhesus monkeys.
Purpose of the Study:
- To establish and characterize animal models for CVB3-induced HFMD.
- To evaluate the susceptibility of Syrian hamsters and rhesus monkeys to CVB3 infection.
- To provide models for studying HFMD pathogenesis and evaluating interventions.
Main Methods:
- Syrian hamsters were infected with CVB3 via intraperitoneal injection and nasal drip.
- Rhesus monkeys were infected with CVB3 via nasal drip.
- Infection outcomes were assessed through clinical signs, pathological examination, viral detection, and serological analysis.
Main Results:
- CVB3 infection was established in Syrian hamsters, causing nasopharyngeal colonization, severe pathology, and HFMD symptoms, with nasal drip leading to more severe outcomes.
- Rhesus monkeys infected with CVB3 displayed HFMD symptoms, viral shedding, antibody response, and organ damage (especially cardiac), but with mild clinical presentation.
- The study successfully developed severe hamster and mild monkey models for CVB3-induced HFMD.
Conclusions:
- Syrian hamsters and rhesus monkeys are susceptible to CVB3 infection, developing HFMD.
- These models offer distinct clinical severities (severe in hamsters, mild in monkeys) for studying CVB3 pathogenesis.
- The developed models are valuable for pre-clinical research, prevention strategies, and post-exposure intervention studies for HFMD.
