| Enterovirus 71 (EV71) has emerged as a major cause of neurological threat in the world following the eradication of poliovirus.EV71 is one of the main causative agents of hand, foot and mouth disease (HFMD).The epidemic of HFMD does serious harm to the health of children in China, in particular,it can cause severe central nervous system (CNS) diseases. HFMD is spread from person-to-person by direct contact with infectious virus, which can be found in nose and throat secretions,saliva, blister fluid, and stool of infected persons,most infected patients are under 10 years old. HFMD caused by EV71 is usually characterized by vesicular lesions on the hand,foot and oral mucosa and can also present with a high rate of neurological complications, including myocarditis, pulmonary edema, meningoencephalitis, aseptic meningitis, encephalitis.Although many clinical study has been reported, however, basic research in HFMD is still not sufficient, especially the clinical treatment of drug and vaccine development lags behind. The basic research of EV71 is extremely urgent and meaningful under the public health situation that the current trend of high incidence of HFMD.In this paper, we use the EV71-FY23 strains that were adapted to Vero cells and KMB17 cells respectively to infect Vero cells and KMB17 cells.Then,these cells were respectively treated with recombinant human IFN-α1b,IFN-λ1 or IFN-γbefore EV71 infection. The results showed that both IFN-a1b and IFN-λ1 have the ability to protect Vero cells and KMB17 cells from EV71 infection in vitro, but IFN-y exerts a worse protective effect than IFN-a1b or IFN-λ1.We also established an animal model of EV71 infection of suckling mice, in this model 1 day old ICR suckling mice were sensitive to the FY23 strains that were isolated from clinical specimen. The first 4 days from the infection, suckling mice displayed weakness, weight loss, arched back, rear-limb paralysis and other symptoms, all mice died within 10 days.the mortality was 100%. Then, we studied the role of IFN-a1b, IFN-λ1, IFN-γ, IL-6 and IL-1βin the process of ICR suckling mice infected with EV71. The results of viral pathology and tissue virus load showed that IFN-alb exerts a better protective effect than IFN-y or IFNM,but the survival rate of IFN-treated mice of all three groups was higher in comparison with other groups. IL-1βand IL-6 are members of Interleukin family, IL-1βcan also protect suckling mice from EV71 infection,but IL-6 exerts no protection but speed up the death of suckling mice. We also examined IL-6 levels in the blood and cerebrospinal fluid (CSF) of rhesus monkeys infected with EV71, the amount of IL-6 increased gradually until 10 day post-infection. Another study also detected IL-1βand IL-6 to be higher in EV71 patients. we hypothesized that these two factors may be contribute to EV71 caused serious damage to CNS.We analyzed the virus load in tissues of IFNs-treated mice before EV71 infection and detected the virus load in brain, spinal cord and hind legs skeletal muscle, virus load in brain of IFNs-treated mice lower than infected-mice, while virus load in spinal cord and skeletal muscle of IFN-treated mice slightly lower than infected-mice. The results of histopathological showed that no lesions were observed in the brain of IFNs-treated mice in contrast to some neurocyte turned up loss, apoptosis of infected-mice. IFNs has an inhibition effect on EV71 replication, and also shape both viral pathogenicity and tissue tropism. It was concluded that IFNs play an important role in controlling EV71 infection. |
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