Characterization of VP1 sequence of Coxsackievirus A16 isolates by Bayesian evolutionary method

Abstract

Background: Coxsackievirus A16 (CV-A16), a major etiopathologic cause of pediatric hand, foot, and mouth disease (HFMD) worldwide, has been reported to have caused several fatalities. Revealing the evolutionary and epidemiologic dynamics of CV-A16 across time and space is central to understanding its outbreak potential.

Methods: In this study, we isolated six CV-A16 strains in China's Jilin province and construct a maximum clade credibility (MCC) tree for CV-A16 VP1 gene by the Bayesian Markov Chain Monte Carlo method using 708 strains from GenBank with epidemiological information. The evolution characteristics of CV-A16 VP1 gene was also analysed dynamicly through Bayesian skyline plot.

Results: All CV-A16 strains identified could be classified into five major genogroups, denoted by GI-GV. GIV and GV have co-circulated in China since 2007, and the CV-A16 epidemic strain isolated in the Jilin province, China, can be classified as GIV-3. The CV-A16 genogroups circulating recently in China have the same ancestor since 2007. The genetic diversity of the CV-A16 VP1 gene shows a continuous increase since the mid-1990s, with sharp increases in genetic diversity in 1997 and 2007 and reached peak in 2007. Very low genetic diversity existed after 2010. The CV-A16 VP1 gene evolutionary rate was 6.656E-3 substitutions per site per year.

Conclusions: We predicted the dynamic phylogenetic trends, which indicate outbreak trends of CV-A16, and provide theoretical foundations for clinical prevention and treatment of HFMD which caused by a CV-A16.

Keywords: Bayesian method; Coxsackievirus A16; Genetic diversity; HFMD; Molecular evolution.

Fig. 1

The maximum clade credibility (MCC) tree was estimated by Bayesian analysis of 708 CV-A16 complete VP1 sequences between 1951 and 2013. The phylogeny include 6 sequences from our laboratory as well as 702 sequences from GenBank with known collection dates and isolate country. Branches arecolor-coded according to the different genogroups. All sequences were classified into five genogroups, denoted GI–GV, Further, genogroup GIV could be divided into sub-genogroups GIV-1, GIV-2, and GIV-3. For the year and isolate country for each sequence, see Additional file 4: Figure S2 in the supplemental material

Fig. 2

Phylogenetic analysis of CV-A16 from Japan. The scale is in units of evolutionary time in years. Phylogenetic tree of 255 Japan strains from 1981 to 2010. The branches of sequences from Japan are highlighted in purple

Fig. 3

Phylogenetic analysis of CV-A16 from Malaysia. The scale is in units of evolutionary time in years. Phylogenetic tree of 81 Malaysia strains from 1998 to 2007. The branches of sequences from China are highlighted in blue

Fig. 4

Phylogenetic analysis of CV-A16 from China. The scale is in units of evolutionary time in years. Phylogenetic tree of 81 China strains from 2000 to 2013. The branches of sequences from China are highlighted in red

Fig. 5

Origin and distribution of CV-A16 from Japan, Malaysia, and China. Different background colors distinguish countries. The blue color depicts Japan (n = 255), and green and pink colors display Malaysia (n = 82) and China (n = 315), respectively

Fig. 6

The genetic diversity dynamics of the CV-A16 VP1 gene estimated by a Bayesian skyline plot through time. A dashed line indicates the mean, whereas shaded areas show the upper and lower 95 % HPD values. The horizontal axis is in the unit year, and the vertical axis is the Net (the product of the effective population size and the generation length in radiocarbon years). The plot for CV-A16 VP1 shows a continuous increase since the mid-1990s, with sharp increases in genetic diversity in 1997 and 2007. Very low genetic diversity existed in the early 1990s and in 2010