Abstract
ABSTRACT Coxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.
Highlights
Coxsackievirus A4 (CVA4) belongs to the family Picornaviridae, genus Enterovirus of linear, non-enveloped, positive polarity single-stranded RNA viruses, which principally cause herpangina and hand, foot and mouth disease (HFMD) in children [1]
Prior to 2009, viral pathogens associated with HFMD included enterovirus A71 (EVA71) and CVA16; in recent years, other types of enteroviruses (EVs), such as CVA4, CVA6 and CVA10 have increased in prevalence [2,3]
We have evaluated the antiviral effects of immune sera and the protective effects of cytokines and maternal antibodies against CVA4
Summary
Coxsackievirus A4 (CVA4) belongs to the family Picornaviridae, genus Enterovirus of linear, non-enveloped, positive polarity single-stranded RNA viruses, which principally cause herpangina and hand, foot and mouth disease (HFMD) in children [1]. Numerous outbreaks of CVA4 have occurred during recent years in different regions in China, such as Fujian [4], Shandong [5, 6], Sichuan [7], Yunnan [8], and Jiangsu [9]. Other countries, such as Thailand [2, 10], Australia [11] and Italy [12] have reported CVA4 infections. Given the increased frequency of CVA4 circulation globally [11, 16, 17], evidence for complex spatiotemporal dynamics in Asia-Europe [18] and the emergence of novel CVA recombinants with the potential to spread rapidly in immunologically naïve populations [13], greater focus is required both on surveillance and the development of prophylactic and therapeutic approaches
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
