Genetic Evolution of Human Enterovirus A71 Subgenotype C4 in Shenzhen, China, 1998 -2013.

Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China.A total of 3,760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, genetic sequences were obtained, and amino acids mutation frequency was calculated. There were 2,040 China nationwide sequences downloaded from Genebank as replication data.In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic outbreak in Shenzhen. Analysis of the nationwide data replicated the same trend of mutation prevalence of the three sites.The switching from Q to H on site 22 of the EV-A71 VP1 strain might be associated with the HFMD outbreak in Shenzhen in 2008. The mutation prevalence map ofChinaprovided a genetic epidemiology picture of EV-A71, showing that the virus might have been transmitted from the Northern part to coastal areas and, finally, inland regions inChina. The identified amino acid sites 22, 283 and 289 provided offered important information for developing anti-viral drugs against EV-A71 in the future.