Limits...
Molecular analysis of virulent determinants of enterovirus 71.

Li R, Zou Q, Chen L, Zhang H, Wang Y - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beijing Center for Disease Control and Prevention, Beijing, China. lirenqingz@sina.com

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198388&req=5

pone-0026237-g001: 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.

Mentions: Phylogenetic analysis of our five EV71 strains and 51 EV71 strains with identified backgrounds from GenBank database was performed by neighbor-joining method based on VP1 coding region (891 nucleotides) or complete polyprotein coding region (6582 nucleotides). Results showed the 25 SC-EV71 and 31 MC-EV71 strains can be divided into three distinct genotypes A, B (including B1 to B5) and C (C1 to C4) (Figure 1). Results based on VP1 coincide with results based on polyprotein perfectly, except strain TW/2272/98, which was isolated from a patient died of pulmonary hemorrhage and shock in Taiwan in 1998. This strain was grouped as subgenotype C2 based on polyprotein, but was subsequently repositioned out of genotype B and genotype C when tested by VP1. Our five strains were all subdivided into C4 subgenotype in the phylogenetic trees (Figure 1).


Molecular analysis of virulent determinants of enterovirus 71.

Li R, Zou Q, Chen L, Zhang H, Wang Y - PLoS ONE (2011)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198388&req=5

pone-0026237-g001: 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.
Mentions: Phylogenetic analysis of our five EV71 strains and 51 EV71 strains with identified backgrounds from GenBank database was performed by neighbor-joining method based on VP1 coding region (891 nucleotides) or complete polyprotein coding region (6582 nucleotides). Results showed the 25 SC-EV71 and 31 MC-EV71 strains can be divided into three distinct genotypes A, B (including B1 to B5) and C (C1 to C4) (Figure 1). Results based on VP1 coincide with results based on polyprotein perfectly, except strain TW/2272/98, which was isolated from a patient died of pulmonary hemorrhage and shock in Taiwan in 1998. This strain was grouped as subgenotype C2 based on polyprotein, but was subsequently repositioned out of genotype B and genotype C when tested by VP1. Our five strains were all subdivided into C4 subgenotype in the phylogenetic trees (Figure 1).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beijing Center for Disease Control and Prevention, Beijing, China. lirenqingz@sina.com

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.

Show MeSH
Related in: MedlinePlus