Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1-11 day post infection) and recovery period (12-180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 patho-physiology and assessing the development of potential human therapies.

Automated summary

This study used rhesus macaques to mimic hand, foot and mouth disease (HFMD) in humans and found that during acute infection, the macaques showed viremia and clinical symptoms similar to those in humans, as well as significant inflammatory pathological damages in multiple organs. During the recovery period, some animals developed severe hyperglycemia due to inflammatory factors. The findings suggest that rhesus macaques can serve as a non-human primate animal model for studying the pathophysiology of CV-A10 and evaluating potential human therapies.