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@#Hand-foot-mouth disease(HFMD) is an infectious disease that seriously affects the health of infants and young children and has become a major public health problem worldwide,especially in the Asia-Pacific region.HFMD can be caused by a variety of enteroviruses,the most common being enterovirus 71(EV71) and Coxsackievirus A16(CVA16).In recent years,with the significant increase of HFMD caused by Coxsackievirus A6(CVA6) infection,CVA6 has gradually become the main pathogen of HFMD in many countries and regions around the world.CVA6 is not only susceptible to children,but also infects adults with normal immune function.The paper reviewed the CVA6 related etiology,epidemiology,clinical symptoms,laboratory diagnosis and development of vaccine.
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@#ObjectiveTo analyze the genome-wide characteristics of 17 strains of Coxsackievirus A6(CVA6)that cause hand,foot and mouth disease(HFMD)and herpangina(HA)in Yunnan Province in 2018,and understand the genetic differences between different pathogenic CVA6.MethodsA total of 1 909 stool samples clinically diagnosed as HFMD and HA in Kunming Children′s Hospital in 2018 were randomly selected for detection using enterovirus group A universal primers and screening of CVA6 positive samples. The CVA6 whole genome sequence was amplified with CVA6 whole genome primers,spliced by BioEdit splicting software,and analyzed for the whole genome characteristics by BioEdit,MEGA 7.0,Simplot,Heml 1.0 and Phyre2softwares.ResultsA total of 929 CVA6 positive samples were screened,and 17CVA6 complete gene sequences were obtained(9 of which were clinically diagnosed as HFMD and 8 were clinically diagnosed as HA). All 17 CVA6 strains were in type IV clade on the whole phylogenetic tree. No significant recombination occurred in HA and HFMD representative strains,while mutations occurred in non-structural protein 3D region. HFMD and HA representative strains showed differences in VP1 loci S597T,Q705L and Q663L. Online predictive analysis showed that the secondary structure of VP1 was consistent with that of CVA6 with no change.ConclusionThe 17 CVA6 strains causing HFMD and HA had high genomic homology,as well as nucleotide and amino acid differences,which may affect the replication and adaptability of CVA6.
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Objective To analyze the biological characteristics of clinical isolates of coxsackievir-us A6 (CVA6), a pathogen of hand,foot and mouth disease (HFMD), and to provide reference for vaccine development. Methods CVA6 strains were isolated from 21 stool and throat swab specimens of patients with HFMD in Yunnan Province and then identified. Their growth characteristics, plaque morphology and virulence to suckling mice were analyzed. Results Five CVA6 strains, named CVA6-129, CVA6-113, CVA6-57, CVA6-94 and CVA6-162, were isolated and all belonged to D3 subtype. Only the CVA6-129 strain could proliferate rapidly in Vero and KMB17 cells and the proliferation peaked 30 h after inoculation. The infectious titer of the CVA6-129 strain was 7. 54 lgCCID50 (50％ cell culture infective dose) / ml in KMB17 cells. Different morphologies of plaques were formed by the CVA6-129 strain in Vero and KMB17 cells at the same time points, which were small and round with clear edges in Vero cells, and large and irregular with blurry edges in KMB17 cells. Suckling mice were susceptible to CVA6 via intramuscular and intraperito-neal injection. The most common symptoms in infected suckling mice were reduced mobility, hind limb pa-ralysis and quadriplegia. CVA6 infection could result in death in severe cases. Conclusions This study isolated five CVA6 strains from a number of clinical samples of suspected HFMD cases, of which the CVA6-129 strain showed potential as a vaccine candidate.
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Objective@#To analyze the etiological of herpangina(HA) in Guangzhou City in 2015, and to provide laboratory data for the epidemic control.@*Methods@#Two hundred and eleven herpangina samples (stool and throat swab) were collected.Real-time (RT)-PCR and semi-nested (Sn)-PCR assays were performed to detect human enteroviruses (HEVs)-positive samples. The human rhabdomyosarcoma (RDa) cell lines were used to inoculate virus from HEVs-positive samples. The entire sequences of viral genes encoding VP1 of CVA6 positive samples or strains were amplified and sequenced. The phylogenetic analysis was performed to analyze the full-length gene sequences encoding VP1 of CVA6 by using DNAStar6.0 and MEGA5.2 software packages.@*Results@#According to the laboratory test results, 115 cases were HEVs-positive and positive rate was 93.50%, eight serotypes of EV including CVA6, CVA10, CVA2, EV71, CVA16, CVB2, Echo14 and Echo30 were detected.The CVA6 positive rate was the highest with a percentage of 60.98%, followed by CVA10 with a percentage of 13.01%. The enterovirus positive rate of stool samples (χ2=29.88, P<0.01) and viruses isolated positive rate (χ2=8.67, P<0.01) were higher than that in throat swab samples. Phylogenetic analysis showed that all CVA6 strains detected in this study belonged to D3 subgenotype, and shared 96.9%-99.9% homologies in nucleotide and 99.0%-100.0% in amino acid.@*Conclusions@#CVA6 of the enterovirus A group accounted for the main pathogen of herpangina in Guangzhou City in Guangdong province in 2015, which belonged to D3 subgenotype.
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This study bioinformatically analyzed the non-VP1 capsid proteins (VP2-VP4) of Coxasckievirus A6 (CVA6), with an attempt to predict their basic physicochemical properties, structural/functional features and linear B cell eiptopes. The online tools SubLoc, TargetP and the others from ExPASy Bioinformatics Resource Portal, and SWISS-MODEL (an online protein structure modeling server), were utilized to analyze the amino acid (AA) sequences of VP2-VP4 proteins of CVA6. Our results showed that the VP proteins of CVA6 were all of hydrophilic nature, contained phosphorylation and glycosylation sites and harbored no signal peptide sequences and acetylation sites. Except VP3, the other proteins did not have transmembrane helix structure and nuclear localization signal sequences. Random coils were the major conformation of the secondary structure of the capsid proteins. Analysis of the linear B cell epitopes by employing Bepipred showed that the average antigenic indices (AI) of individual VP proteins were all greater than 0 and the average AI of VP4 was substantially higher than that of VP2 and VP3. The VP proteins all contained a number of potential B cell epitopes and some eiptopes were located at the internal side of the viral capsid or were buried. We successfully predicted the fundamental physicochemical properties, structural/functional features and the linear B cell eiptopes and found that different VP proteins share some common features and each has its unique attributes. These findings will help us understand the pathogenicity of CVA6 and develop related vaccines and immunodiagnostic reagents.