The variations of VP1 protein might be associated with nervous system symptoms caused by enterovirus 71 infection

BACKGROUND The VP1 protein of enterovirus 71 (EV71) is an important immunodominant protein which is responsible for host-receptor binding. Nevertheless, the relationship between VP1 and neurovirulence is still poorly understood. In this study, we investigated the relationship between mutation of VP1 and neurovirulent phenotype of EV71 infection. METHODS One hundred and eighty-seven strains from Genbank were included, with a clear clinical background. They were divided into two groups, one with nervous system symptoms and one with no nervous system symptoms. After alignment, the significance of amino acid variation was determined by using the χ2 test and a phylogenetic tree was constructed with MEGA software (version 5.1). RESULTS We showed no significant difference in neurovirulence between genotype B and C. Interestingly, we found that variations of E145G/Q, E164D/K and T292N/K were associated with nervous system infection in genotype B. In the case of genotype C, the N31D mutation increased the risk for nervous complications, whereas I262V mutation decreased the risk of nervous complications. We used a 3D model of VP1 to demonstrate the potential molecular basis for EV71 nervous system tropism. CONCLUSIONS Distinct variations are shown to be associated with neurovirulent phenotype in the different genotype. Detection of variation in genotypes and subtypes may be important for the prediction of clinical outcomes.