The variations of VP1 protein might be associated with nervous system symptoms caused by enterovirus 71 infection - PubMed (original) (raw)

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

Bao Zhang et al. BMC Infect Dis. 2014.

Abstract

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.

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Figures

Figure 1

Figure 1

Phylogenetic dendrogram constructed by using complete VP1 gene sequence of 187 EV71 strains. Genotypes and subtypes are shown on the right, and bootstrap values (percentage of 1,000 pseudoreplicates) are shown at the nodes of the major clades. All subtypes branches are combined except for strain AF135899.

Figure 2

Figure 2

Location of amino acids in the 3D structure of VP1 protein (A) and the complex (B) of VP1, VP2 and VP3. A and B are based on the PDB 3VBS which belonged to genotype C. the structure of PDB 3VBS was reconstituted with software of Cn3D (version 4.3.1).The consensus residues of K43, A58, S184 and T240 and canyon structure are shown in A; the variation sites of N31, E145, D164, I262 and T292 of VP1, F149 of VP2 are shown in B.

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