Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008

Abstract

Coxsackievirus A2 (CV-A2) has been frequently detected and commonly associated with hand, foot, and mouth disease (HFMD) in China since 2008. However, limited sequences of CV-A2 are currently available. As a result, we have been focusing on the genetic characteristics of CV-A2 in the mainland of China during 2008–2015 based on national HFMD surveillance. In this study, 20 CV-A2 strains were isolated and phylogenetic analyses of the VP1 sequences were performed. Full-length genome sequences of two representative CV-A2 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CV-A2 strains could be divided into four genotypes (Genotypes A–D). The CV-A2 prototype strain (Fleetwood) was the sole member of genotype A. From 2008 to 2015, the CV-A2 strains isolated in China dispersed into two different genotypes (B and D). And the genotype D became the dominant circulating strains in China. Strains isolated in Russia and India from 2005 to 2011 converged into genotype C. Intertypic recombination occurred between the Chinese CV-A2 strains and other enterovirus-A donor sequences. This result reconfirmed that recombination is a common phenomenon among enteroviruses. This study helps expand the numbers of whole virus genome sequence and entire VP1 sequence of CV-A2 in the GenBank database for further researcher.

Persistent circulation of genotype D coxsackievirus A2 in mainland of China since 2008

“…Previous studies have classified CV-A2 into four genotypes, namely, genotypes A, B, C, and D, in which genotypes are distinguished based on least 15% divergence in the VP1 nucleotide sequence [ 12 ]. Genotype C can be further divided into the C1 to C3 sub-genotypes, which exhibit more than 8% divergence in the VP1 region [ 18 ].…”

“…In this study, we expanded the surveillance scope in that collected 74 new strains which were not included in HFMD cases isolated in previous study [ 12 ], and accomplished a more comprehensive molecular epidemiological analysis of CV-A2 from all six regions in mainland of China, and analyzed based on a long time span of 2008–2017. Earlier studies have classified CV-A2 into four genotypes, genotypes A, B, C, and D. In this study, we further divided genotype C into the C1 to C3 sub-genotypes in order to better explain genotype C. According to the previous genotyping rules, all 74 strains isolated in the present study were grouped under genotype D. Interestingly, genotype D was only found in China since 2008, which need continuous surveillance.…”

“…Reverse transcription polymerase chain reaction (RT-PCR) was performed to amplify the entire VP1 capsid region (885 nucleotides) using PrimeScript One Step RT-PCR Kit Ver. 2 (TaKaRa, Dalian, China) and previously designed primers (forward (486 or CV-A2-2787-S) and reverse (488 or CV-A2-3618-A) primers) [ 12 ]. Preparation of RT-PCR reactions and amplification profiles were based on previously reported protocols.…”

Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

“…For E6, CVA2, CVA13, E7, CVA2 and EV-A71 the sequences D'Amori (AY302558.1), Fleetwood (AY421760.1), Flores (AF499637.1), Wallace (AF465516.1), Faulkner (AF114383.1) and BrCr (U22511) were used as reference strains, respectively. Reference sequences for viral genogroups, genotypes and/or clusters were also included [17,[20][21][22]. VP1 sequences were edited using Bioedit (7.2.5.0)/SeqMan (7.0.0) programs and aligned by Muscle [23].…”

Outbreak of recombinant coxsackievirus A2 infection and polio-like paralysis of children, Taiwan, 2014

“…2), and a study in China reported a similar situation. 7 In conclusion, we report a recombinant CVA2 isolated from children with AFP in Taiwan. Because the CVA2 has an outbreak potential, and this CVA2 strain has a high risk of unfavorable neurological outcomes, children with AFP should be examined for the presence of CVA2 and other pathogenic EVs.…”