Study Of Human Enterovirus71(EV71)2A Protease Resisted Type Ⅰ Interferon Induced Antiviral Effect

Hand-foot-mouth disease (HFMD) is a global epidemic which is caused by a variety of enterovirus. It occurs more often in children under the age of five and is characterized by skin rash with blisters on the palms of the hands, soles of the feet, in the mouth and on buttocks. HFMD is only a mild infection in general, and even though young children and adults are asymptomatic carriers, yet they are potential contagious sources of the virus. The usual course of the disease is7to10days, and once affected, some children are liable to complications of myocarditis, pulmonary edema and aseptic meningitis, and may be fatal due to the seriously rapid progression of the disease.In terms of epidemiologic investigation, HFMD caused by enterovirus is most often associated with Coxsackie virus A16(CoxA16) and enterovirus71(EV71). Cases of CoxA16infection are sporadic and may lead to fewer outbreaks, thus to better prognosis, whereas EV71may cause much severer cases and higher mortality.The innate immune, also known as non-specific immune system, is not antigen specific and reacts equally well to a variety of organisms. It has an important role that plays in the defense mechanisms of a body, acts as the first line of defense and comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner.Type I interferon synthesis and secretion is a vitally important aspect of innate immune response. Type I interferon is early produced during viral infection and induces antiviral effects within target cells and mediate the development of the innate and adaptive immune responses, and its production is triggered when cells detect viral RNA by specific receptors intracellular for RNA virus, thus triggering a signal cascade effect and eventually inducing target cells to produce specific anti-viral protein.Characteristically, the usual incubation period after EV71infection is between2and7days, and3to5days for fetal cases. Such short course will certainly cause failure of adaptive immune response to EV71. Accordingly, it is believed that innate immune response may play an important role in critically severe and fatal HFMD cases. In order to understand the role of type I interferon in the process of innate immune response during EV71infection, this study was designed to assess the function of both a-and P-interferon associated with type I interferon through recombinant herpes simple virus (HSV-1) expression with green fluorescent protein (GFP). We initially inoculated both α-and β-interferon into the HeLa cells to induce the GFP expression via HSV-1proliferation inhibition, and our findings revealed that EV71had inhibited the proliferation of HeLa cells, suggesting that EV71may resist the antiviral material induced from type I interferon.To further interpret the mechanisms of EV71against type I interferon, we transiently expressed EV712A protease into the HeLa cells incubated with type I interferon (α,β), and found that HSV-1replication was enhanced in GFP expression, which suggested that EV71may free itself through protection of type I interferon in host and thus lead to persistent infection.