Virology
Sequence analysis of VP1-VP4 genes of coxsackievirus A6 strains isolated from children with severe hand, foot, and mouth disease in Shenzhen from 2012 to 2015
Xiangjie Yao, Long Chen, Weiqi Wang, Hong Yang, Jun Meng, Hailong Zhang, Yaqing He, Renli Zhang, Shaojian Xu
Published 2019-01-31
Cite as Chin J Microbiol Immunol, 2019, 39(1): 24-29. DOI: 10.3760/cma.j.issn.0254-5101.2019.01.005
Abstract
ObjectiveTo analyze the genetic characteristics of VP1-VP4 genes carried by coxsackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015.
MethodsThe VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6.0 and MEGA6.02 software packages.
ResultsFour cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98.8%-98.9% homology in nucleotide sequences and 99.3%-99.8% in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95.0% homology in nucleotide sequences and 99.3% homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785).
ConclusionsAll CVA6 strains causing severe HFMD cases in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.
Key words:
Hand, foot, and mouth disease; Coxsackievirus A6; Severe case; Genotype; Mutation
Contributor Information
Xiangjie Yao
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Long Chen
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Weiqi Wang
Guangdong Medical University, Dongguan 523808, China
Hong Yang
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Jun Meng
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Hailong Zhang
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Yaqing He
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Renli Zhang
Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Shaojian Xu
Shenzhen Longhua Center for Disease Control and Prevention, Shenzhen 518109, China
