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. 2015 Feb;4(2):e12.
doi: 10.1038/emi.2015.12. Epub 2015 Feb 25.

Phylogenetic analysis of the major causative agents of hand, foot and mouth disease in Suzhou City, Jiangsu province, China, in 2012-2013

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Phylogenetic analysis of the major causative agents of hand, foot and mouth disease in Suzhou City, Jiangsu province, China, in 2012-2013

Chao Zhang et al. Emerg Microbes Infect. 2015 Feb.

Abstract

Hand, foot and mouth disease (HFMD) is a serious public health problem that has emerged over the past several decades. Pathogen detection by the Chinese national HFMD surveillance system has focused mainly on enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Therefore, epidemiological information regarding the other causative enteroviruses is limited. To identify the pandemic enterovirus in Suzhou, Jiangsu province, China, clinical samples from patients with HFMD were collected from 2012 to 2013 and analyzed. The results revealed that CA16 was the most dominant HFMD pathogen in 2012, whereas CA6 and CA10 were the dominant pathogens in 2013. Phylogenetic analysis revealed that the C4a sub-genogroup of EV71 and the B1a and B1b sub-genogroups of CA16 continued to evolve and circulate in Suzhou. The CA6 strains were assigned to six genotypes (A-F) and the CA10 strains were assigned to seven genotypes (A-G), with clear geographical and temporal distributions. All of the CA6 strains in Suzhou belonged to genogroup F, and there were several lineages circulating in Suzhou. All of the CA10 strains in Suzhou belonged to genogroup G, and they had the same genetic origin. Co-infections of EV71/CA16 and CA6/CA10 were found in the samples, and bootscan analysis of 5'-untranslated regions (UTRs) revealed that some CA16 strains in Suzhou had genetic recombination with EV71. This property might allow CA16 to alter its evolvability and circulating ability. This study underscores the need for surveillance of CA6 and CA10 in the Yangtze River Delta and East China.

Keywords: CA10; CA16; CA6; EV71; co-infection; genetic recombination; hand, foot and mouth disease.

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Figures

Figure 1
Figure 1
Geographical location of Suzhou in the Yangtze River Delta.
Figure 2
Figure 2
Phylogenetic dendrograms based on the partial VP1 nucleotide sequences of EV71. The dendrograms were constructed using the neighbor-joining method based on the alignment of the partial VP1-region sequences of Suzhou strains and other strains downloaded from GenBank. Bootstrap values (%) for 1000 replicates were calculated, and only values >70% are shown at the nodes. Red dots indicate Suzhou EV71 strains, and the CA16 strain (TW-00190) was used as an out-group. The descriptions in the brackets following the strains downloaded from GenBank indicate the sub-genogroup of each strain.
Figure 3
Figure 3
Phylogenetic dendrograms based on the partial VP1 nucleotide sequences of CA16. The dendrograms were constructed using the neighbor-joining method based on the alignment of the partial VP1-region sequences of Suzhou strains and other strains downloaded from GenBank. Bootstrap values (%) for 1000 replicates were calculated, and only values >70% are shown at the nodes. Red dots indicate Suzhou CA16 strains, and the EV71 strain (H8-1) was used as an out-group.
Figure 4
Figure 4
Phylogenetic dendrograms based on partial VP1 nucleotide sequences of CA6. The dendrograms were constructed using the neighbor-joining method based on the alignment of the partial VP1-region sequences of Suzhou strains and other strains downloaded from GenBank. Bootstrap values (%) for 1000 replicates were calculated, and only values >70% are shown at the nodes. Red dots indicate the CA6 isolates of Suzhou. Green rhombuses indicate the CA6 isolates of Shanghai collected from GenBank. The Suzh058-CA10 strain identified in this study was used as an out-group.
Figure 5
Figure 5
Phylogenetic dendrograms based on partial VP1 nucleotide sequences of CA10. The dendrograms were constructed using the neighbor-joining method based on the alignment of the partial VP1-region sequences of Suzhou strains and other strains downloaded from GenBank. Bootstrap values (%) for 1000 replicates were calculated, and only the values >70% are shown at the nodes. Red dots indicate the CA10 isolates of Suzhou. Green rhombuses indicate the CA10 isolates of Shanghai collected from GenBank. The Suzh001-CA16 strain identified in this study was used as an out-group.
Figure 6
Figure 6
Bootscan analysis of CA16 strains in Suzhou with other types of enteroviruses. The EV71 reference strain was wuhan1143/CHN (JX986739). The CA6 reference strain was NUH0027/SIN (GU198759). The CA10 reference strain was CA10-SD/CHN (HQ728262). The CA16 reference strain was FJ10-03/CHN (KF193626). The CB3 reference strain was Fuyang19/CHN (FJ000001). The PV1 strain was PV1/USA (V01149). The percentage of permutated trees in a sliding 60-bp window with 10-bp steps is represented on the Y-axis. CB3, coxsackievirus B3.

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