Molecular analysis of virulent determinants of enterovirus 71 - PubMed (original) (raw)

Molecular analysis of virulent determinants of enterovirus 71

Renqing Li et al. PLoS One. 2011.

Abstract

Enterovirus 71 (EV71) is the most important causative agent of hand, foot and mouth disease (HFMD) in children. In most cases, it is a self-limiting illness. However some EV71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. To identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 5'-NTR and 3'-NTR in 25 SC-EV71 strains (strains from severe cases) and 31 MC-EV71 strains (strains from mild cases) were analyzed. Results showed four amino acids on two positions (Gly(P710)/Gln(P710)/Arg(P710) and Glu(P729)) on the DE and EF loop of VP1, one (Lys(P930)) on the surface of protease 2A and four nucleotides on three positions (G(P272), U(P488) and A(P700)/U(P700)) in the 5'-NTR region are associated with EV71 virulent phenotype. Predicted secondary structure of RNA using the consensus sequence of 5'-NTR by RNAStructure showed the mutation of nucleotide at position 488 in strain BJ08-Z004-3 (position 491 in prototype strain BrCr) can result in the discrepancy of an additional pair of nucleotides and thus change the stability of the second structure of IRES. Fragment base content analysis showed that in the region 696 to 714 bp at the 5'-NTR, where the A(P700)/U(P700) was located, the nucleotide constitution ratios differed significantly between SC-EV71 and MC-EV71 strains. In conclusion, comparative genomic analysis showed that virulence of EV71 strains are mainly determined by the amino acids on two positions of VP1, one position of protease 2A and the nucleotides on three positions in 5'-NTR.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Phylogenetic analysis of VP1 protein coding region and the complete polyprotein coding region of EV71 strains.

A: phylogenetic tree based on VP1 protein coding region. B: phylogenetic tree based on polyprotein coding region. ▴: SC-EV71 strain.

Figure 2

Figure 2. The predicted three dimensional structures of VP1 protein and protease 2A of EV71.

A: predicted three dimensional structure of VP1 protein. The left yellow ball represents the 145th amino acid residue (P710) at VP1, and the right one represents the 164th residue (P729) at VP1. B: predicted three dimensional structure of Protease 2A protein. The yellow ball represents the 68th residue (P930) at 2A protein. C: the comparison of DE loop between predicted VP1 structure of EV71 (BJ08-Z004-3) and the real structure of 4 other picornaviruses. The yellow tubes represent the DE loop, and the yellow balls represent the corresponding residue on each strain to the residue on VP1-145 of EV71. D: the comparison of EF loop between predicted VP1 structure of EV71 and the real structure of 4 other picornaviruses. The yellow tubes represent the EF loop, and the yellow balls represent the corresponding residue on each strain to the residue on VP1-164 of EV71.

Figure 3

Figure 3. The comparison of 5′NTR secondary structure predicted by RNAStructure between the SC-EV71 and MC-EV71 strain.

A: the whole structural comparison. B: the comparison of specific part of Domain I. C: the comparison of specific part of Domain II. D: the comparison of specific part of Domain III. E: the comparison of specific part of Domain V.

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