The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China

Abstract

Coxsackievirus A10 (CV-A10) associated with Hand, foot, and mouth disease (HFMD) cases emerged increasingly in recent years. In this study, the samples from nation-wide HFMD surveillance, including 27 out of 31 provinces in China were investigated, and the continuous and extensive virological surveillance, covered 13 years, were conducted to provide a comprehensive molecular characterization analysis of CV-A10. 855 CV-A10 viruses (33 severe cases included), were isolated from HFMD children patients during 2009 to 2016 in China. 164 representative sequences from these viruses, together with 117 CV-A10 sequences downloaded from GenBank based on entire VP1 were recruited in this study. Two new genotypes (F and G) and two sub-genotypes (C1 and C2) were identified. Among 264 Chinese sequences, 9 of them were genotype B, 8 of them were C1, and the other (247) were C2, the predominant sub-genotype in China since 2012. Chinese C2 viruses showed obvious temporal characteristics and can be divided into 3 clusters (cluster 1~3). Cluster 3 viruses was circulating extensively during 2014 and 2016 with more severe cases. It is very necessary and important to continuously conduct the extensive virological surveillance for CV-A10, and further evolutionary studies will provide more evidence on its evolution and virulence.

Figure 1

(A) Temporal and geographic distribution of 1044 Chinese CV-A10 viruses during 2004–2016. (B) Number of cases of HFMD by month of illness onset.

Figure 2

Phylogenetic dendrogram was drawn on bases of the 894-nt sequences for 281 representative CV-A10 isolates from 2004–2016. The Striains that isolated from different years were represent by different color according to the legend. Solid triangle indicated the severe cases. Sequences downloaded from GenBank was list in Supplementary Table S1.

Figure 3

Phylogenetic analyses based on all the available partial VP1 (239 bp on the 5′ of VP1 region) of CV-A10 in the world. Representative sequences of entire VP1 selected from different genotypes and time in the world were labeled with solid circle, of which Chinese sequences were labeled with solid red circles.

Figure 4

(A) Yearly and geographic distribution of genotypes and clusters of CV-A10 in china from 2004 to 2016. Different genotypes and clusters were colored according to the legend. (B) The geographic distribution of HFMD associated CV-A10 viruses in 7 representative regions of China. Different regions and numbers were colored according to the legend (Taiwan China sequences were not included). The free map was required from ArcGis.