Abstract
Coxsackievirus A16 (CA16) is one of the main causative pathogens of hand, foot and mouth disease (HFMD). Viral replication typically results in host cell apoptosis. Although CA16 infection has been reported to induce apoptosis in the human rhabdomyosarcoma (RD) cell line, it remains unclear whether CA16 induces apoptosis in diverse cell types, especially neural cells which have important clinical significance. In the current study, CA16 infection was found to induce similar apoptotic responses in both neural cells and non-neural cells in vitro, including nuclear fragmentation, DNA fragmentation and phosphatidylserine translocation. CA16 generally is not known to lead to serious neurological symptoms in vivo. In order to further clarify the correlation between clinical symptoms and cell apoptosis, two CA16 strains from patients with different clinical features were investigated. The results showed that both CA16 strains with or without neurological symptoms in infected patients led to neural and muscle cell apoptosis. Furthermore, mechanistic studies showed that CA16 infection induced apoptosis through the same mechanism in both neural and non-neural cells, namely via activation of both the mitochondrial (intrinsic) pathway-related caspase 9 protein and the Fas death receptor (extrinsic) pathway-related caspase 8 protein. Understanding the mechanisms by which CA16 infection induces apoptosis in both neural and non-neural cells will facilitate a better understanding of CA16 pathogenesis.
Highlights
Hand, foot, and mouth disease (HFMD) is a febrile exanthematous disease mostly prevalent in children younger than 5 years of age
coxsackievirus A16 (CA16) infection generally does not lead to nervous symptoms in the clinic, but here we found that CA16 infection induced apoptosis in non-neural cells and in neural cells in vitro
Evidence of all markers of apoptosis in RD, HepG2, A172 and SK-N-SH cells indicated that CA16 infection induced extensive apoptosis in different cell types including neural cell lines, even though CA16 infection does not lead to nervous symptoms in patients
Summary
Foot, and mouth disease (HFMD) is a febrile exanthematous disease mostly prevalent in children younger than 5 years of age. The symptoms of HFMD are vesicles on the palmar and plantar surfaces of the hands and feet, and on the buccal mucosa, tongue and buttocks [1,2,3]. Both coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are the major pathogens responsible for HFMD, circulating alternatively or together in different years [4,5,6,7,8]. The seroprevalence data in Guangdong Province, China showed that EV71 was responsible for 44.6%, 46.4% and 31.8% of reported cases, while CA16 accounted for 70.3%, 51.6% and 47.3% in 2007, 2008 and 2009, respectively. 32.4% and 29.4% respectively exhibited neutralizing antibodies against both viruses in 2007 and 2008 [9]
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