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Epidemics and Frequent Recombination within Species in Outbreaks of Human Enterovirus B-Associated Hand, Foot and Mouth Disease in Shandong China in 2010 and 2011.

Zhang T, Du J, Xue Y, Su H, Yang F, Jin Q - PLoS ONE (2013)

Bottom Line: Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points.In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup.Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

View Article: PubMed Central - PubMed

Affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy Medical Sciences & Peking Union Medical College, Beijing, China.

ABSTRACT
The epidemiology and molecular characteristics of human enterovirus B (HEV-B) associated with hand, foot and mouth disease (HFMD) outbreaks in China are not well known. In the present study, we tested 201 HEV isolates from 233 clinical specimens from patients with severe HFMD during 2010-2011 in Linyi, Shandong, China. Of the 201 isolates, 189 were fully typed and 18 corresponded to HEV-B species (six serotypes CVA9, CVB1, CVB4, Echo 6, Echo 25 and Echo 30) using sensitive semi-nested polymerase chain reaction analysis of VP1 gene sequences. Phylogenetic analysis based on the VP1 region showed that eight E30SD belonged to a novel sub-genogroup D2; E25SD belonged to a novel sub-genogroup D6; E6SD belonged to sub-lineage C6 and five CVB1SD belonged to subgroup 4C; and B4SD belonged sub-lineage D2. The full viral genomes of the CVB1SD, E6SD, E25SD and E30SD isolates were sequenced. Analysis of phylogenetic and similarity plots indicated that E25SD recombined with E25-HN-2, E30FDJS03 and E4AUS250 at noncontiguous P2A-P3D regions, while E30SD, E30FDJ03, E25-HN-2 and E9 DM had shared sequences in discrete regions of P2 and P3. Both E6SD and B1SD shared sequences with E1-HN, B4/GX/10, B5-HN, and A9-Alberta in contiguous regions of most of P2 and P3. Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points. In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup. Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

No MeSH data available.


Related in: MedlinePlus

SimPlot analyses based on full-length genomes of the newly isolated HEV-B strains and other HEV-B prototype strains.Each of the E25-HN2 and E30-FDJS03-84 sequences was used as the query sequence in each analysis. A sliding window of 400 nt moving in 50-nt steps was used in this analysis. (a) E25SD; (b) E30SD; (c) E25-HN2; (d) E30-FDJS03-84.
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pone-0067157-g009: SimPlot analyses based on full-length genomes of the newly isolated HEV-B strains and other HEV-B prototype strains.Each of the E25-HN2 and E30-FDJS03-84 sequences was used as the query sequence in each analysis. A sliding window of 400 nt moving in 50-nt steps was used in this analysis. (a) E25SD; (b) E30SD; (c) E25-HN2; (d) E30-FDJS03-84.

Mentions: To address the issue of recombination in more detail, the aligned HEV-B complete genome sequences were further analyzed by examining the similarity among sequences in a sliding window of 400 residues, using the SimPlot program. The sequence of each strain was used as the query sequence to generate 40 separate similarity plots. All HEV-B strain 5′NTRs (Figures 8 and 9) were almost equidistant from each other with 85–96% similarity. The VP1 regions of B1SD, E6SD, E25SD and E30SD showed the highest similarities to their prototypes CVB1-conn-5, E6-D′Amori, EV25-JV4, and E30-Bastianni, respectively. CVB5SD, E6SD, E25SD, and E30SD also manifested the highest similarities to their modern strains CVB5-HN, E6-JPN-2011, E25-HN-2, E30FDJ in the 5′ half of the genome (ending around nt 4000–5000 within the P2 region). Interestingly, CVB4/JX/10 was highly similar to at least five other strains, E1-JQ979292, CVB5-HN, E6SD, A9-Alberta, and CVB1 (94–98.7%) throughout most of P2 and P3, in which the similarity plot displayed two obvious cross-points at nts 4667 and 5321 among the five strains (Figure 8a and 8b). The similarity plots for E6SD and CVB1 further confirmed that the CVB1SD, CVB5-HN, CVB4/JX/10, A9-Alberta, E1 and E6SD strains were most similar to each other, with high similarity (94–98.7%) extending from nt 4667 or 5321 to the end of 3D (Figure 8c and 8d). In contrast, E25SD and E30SD exhibited a complicated relationship with the other strains E25-HN, FDJS03, E9-DM and E4-AUS250 in the P3 region. E25SD was closely related to FDJS03 in 2C, 3AB, and part of the 3D region (Figure 9a), whereas it shared the highest similarity with E4AUS250 at the 3C–3D junction region. Similarly, E30SD was related to E25-HN-2 in the 3A–3B region, to EV97 at the 3C–3D junction, and to E9 DM in a portion of 3C with over 95% bootstrap values (Figure 9b). In contrast, the regions of similarity between E25-HN2 and FDJS03 differed from E25SD and E30SD according to the temporal order of strain discovery. E25-HN2 was only related to E4AUS250 in 3D with 90% similarity (Figure 9c), whereas E30-FDJS03 was related to E9 in part of 3C with 85% similarity (Figure 9d). The SimPlot results indicated complex mosaic recombination involving CVB1SD11, E6SD11, CVA9-Alberta-2010, COXB5/Henan/2010, CVB4/GX/10, E1-JQ979292, E25SD, and E30SD.


Epidemics and Frequent Recombination within Species in Outbreaks of Human Enterovirus B-Associated Hand, Foot and Mouth Disease in Shandong China in 2010 and 2011.

Zhang T, Du J, Xue Y, Su H, Yang F, Jin Q - PLoS ONE (2013)

SimPlot analyses based on full-length genomes of the newly isolated HEV-B strains and other HEV-B prototype strains.Each of the E25-HN2 and E30-FDJS03-84 sequences was used as the query sequence in each analysis. A sliding window of 400 nt moving in 50-nt steps was used in this analysis. (a) E25SD; (b) E30SD; (c) E25-HN2; (d) E30-FDJS03-84.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3686723&req=5

pone-0067157-g009: SimPlot analyses based on full-length genomes of the newly isolated HEV-B strains and other HEV-B prototype strains.Each of the E25-HN2 and E30-FDJS03-84 sequences was used as the query sequence in each analysis. A sliding window of 400 nt moving in 50-nt steps was used in this analysis. (a) E25SD; (b) E30SD; (c) E25-HN2; (d) E30-FDJS03-84.
Mentions: To address the issue of recombination in more detail, the aligned HEV-B complete genome sequences were further analyzed by examining the similarity among sequences in a sliding window of 400 residues, using the SimPlot program. The sequence of each strain was used as the query sequence to generate 40 separate similarity plots. All HEV-B strain 5′NTRs (Figures 8 and 9) were almost equidistant from each other with 85–96% similarity. The VP1 regions of B1SD, E6SD, E25SD and E30SD showed the highest similarities to their prototypes CVB1-conn-5, E6-D′Amori, EV25-JV4, and E30-Bastianni, respectively. CVB5SD, E6SD, E25SD, and E30SD also manifested the highest similarities to their modern strains CVB5-HN, E6-JPN-2011, E25-HN-2, E30FDJ in the 5′ half of the genome (ending around nt 4000–5000 within the P2 region). Interestingly, CVB4/JX/10 was highly similar to at least five other strains, E1-JQ979292, CVB5-HN, E6SD, A9-Alberta, and CVB1 (94–98.7%) throughout most of P2 and P3, in which the similarity plot displayed two obvious cross-points at nts 4667 and 5321 among the five strains (Figure 8a and 8b). The similarity plots for E6SD and CVB1 further confirmed that the CVB1SD, CVB5-HN, CVB4/JX/10, A9-Alberta, E1 and E6SD strains were most similar to each other, with high similarity (94–98.7%) extending from nt 4667 or 5321 to the end of 3D (Figure 8c and 8d). In contrast, E25SD and E30SD exhibited a complicated relationship with the other strains E25-HN, FDJS03, E9-DM and E4-AUS250 in the P3 region. E25SD was closely related to FDJS03 in 2C, 3AB, and part of the 3D region (Figure 9a), whereas it shared the highest similarity with E4AUS250 at the 3C–3D junction region. Similarly, E30SD was related to E25-HN-2 in the 3A–3B region, to EV97 at the 3C–3D junction, and to E9 DM in a portion of 3C with over 95% bootstrap values (Figure 9b). In contrast, the regions of similarity between E25-HN2 and FDJS03 differed from E25SD and E30SD according to the temporal order of strain discovery. E25-HN2 was only related to E4AUS250 in 3D with 90% similarity (Figure 9c), whereas E30-FDJS03 was related to E9 in part of 3C with 85% similarity (Figure 9d). The SimPlot results indicated complex mosaic recombination involving CVB1SD11, E6SD11, CVA9-Alberta-2010, COXB5/Henan/2010, CVB4/GX/10, E1-JQ979292, E25SD, and E30SD.

Bottom Line: Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points.In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup.Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

View Article: PubMed Central - PubMed

Affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy Medical Sciences & Peking Union Medical College, Beijing, China.

ABSTRACT
The epidemiology and molecular characteristics of human enterovirus B (HEV-B) associated with hand, foot and mouth disease (HFMD) outbreaks in China are not well known. In the present study, we tested 201 HEV isolates from 233 clinical specimens from patients with severe HFMD during 2010-2011 in Linyi, Shandong, China. Of the 201 isolates, 189 were fully typed and 18 corresponded to HEV-B species (six serotypes CVA9, CVB1, CVB4, Echo 6, Echo 25 and Echo 30) using sensitive semi-nested polymerase chain reaction analysis of VP1 gene sequences. Phylogenetic analysis based on the VP1 region showed that eight E30SD belonged to a novel sub-genogroup D2; E25SD belonged to a novel sub-genogroup D6; E6SD belonged to sub-lineage C6 and five CVB1SD belonged to subgroup 4C; and B4SD belonged sub-lineage D2. The full viral genomes of the CVB1SD, E6SD, E25SD and E30SD isolates were sequenced. Analysis of phylogenetic and similarity plots indicated that E25SD recombined with E25-HN-2, E30FDJS03 and E4AUS250 at noncontiguous P2A-P3D regions, while E30SD, E30FDJ03, E25-HN-2 and E9 DM had shared sequences in discrete regions of P2 and P3. Both E6SD and B1SD shared sequences with E1-HN, B4/GX/10, B5-HN, and A9-Alberta in contiguous regions of most of P2 and P3. Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points. In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup. Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

No MeSH data available.


Related in: MedlinePlus