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...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 Sub Loc, Target P and the others from Ex PASy 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.展开更多
本研究旨在通过对手足口病(Hand,foot and mouth disease,HFMD)病例的病原学标本进行肠道病毒分型鉴定,和对CVA6和CVA10开展VP1基因全长序列分析,探究广东省汕头市HFMD病原谱及CVA6和CVA10基因进化特征,为当地HFMD肠道病毒监测及预警提...本研究旨在通过对手足口病(Hand,foot and mouth disease,HFMD)病例的病原学标本进行肠道病毒分型鉴定,和对CVA6和CVA10开展VP1基因全长序列分析,探究广东省汕头市HFMD病原谱及CVA6和CVA10基因进化特征,为当地HFMD肠道病毒监测及预警提供一定的技术支撑。将汕头市病原监测哨点医院2018-2021年的HFMD样本进行RT-PCR肠道病毒病原学分型,筛选出CVA6和CVA10样本进行VP1区全长基因扩增和测序,并通过系统进化分析、同源性和突变位点分析了解其遗传进化特征。结果显示,2018-2021年共监测到HFMD阳性样本706份,其主要病原体为CVA6和CVA10。CVA6和CVA10流行株分别属于D3和C2亚型。CVA6样本VP1核苷酸和氨基酸的相似性分别为91.37%~100.00%和92.79%~100.00%,与2010年的中国台湾株高度同源(GenBank:JQ946055.1)。CVA10样本VP1核苷酸和氨基酸的相似性分别为92.28%~100.00%和96.98%~100.00%,与2014年的广东株高度同源(GenBank:MN451243.1)。与同型别原型株相比,CVA6样本有2个高频的非同义氨基酸突变位点造成了氨基酸极性或带电性的改变(F305S、T14A),CVA10样本则有9个(D25N、A33T、F148Y、Q223L、A291S、A78T、N27E、V240E、V107T)。以上结果提示当地需密切关注病毒流行谱和动态监测HFMD患者临床症状,以防病毒蛋白结构和功能的改变,加重其毒性和感染力。展开更多
Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can...Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.展开更多
基金supported by the National Natural Science Foundation of China(No.81460304)Guangxi Natural Science Foundation(No.2015GXNSFDA139020)a research program sponsored by the Health Bureau of Guangxi Zhuang Autonomous Region,China(No.Z2014298)
文摘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 Sub Loc, Target P and the others from Ex PASy 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.
文摘本研究旨在通过对手足口病(Hand,foot and mouth disease,HFMD)病例的病原学标本进行肠道病毒分型鉴定,和对CVA6和CVA10开展VP1基因全长序列分析,探究广东省汕头市HFMD病原谱及CVA6和CVA10基因进化特征,为当地HFMD肠道病毒监测及预警提供一定的技术支撑。将汕头市病原监测哨点医院2018-2021年的HFMD样本进行RT-PCR肠道病毒病原学分型,筛选出CVA6和CVA10样本进行VP1区全长基因扩增和测序,并通过系统进化分析、同源性和突变位点分析了解其遗传进化特征。结果显示,2018-2021年共监测到HFMD阳性样本706份,其主要病原体为CVA6和CVA10。CVA6和CVA10流行株分别属于D3和C2亚型。CVA6样本VP1核苷酸和氨基酸的相似性分别为91.37%~100.00%和92.79%~100.00%,与2010年的中国台湾株高度同源(GenBank:JQ946055.1)。CVA10样本VP1核苷酸和氨基酸的相似性分别为92.28%~100.00%和96.98%~100.00%,与2014年的广东株高度同源(GenBank:MN451243.1)。与同型别原型株相比,CVA6样本有2个高频的非同义氨基酸突变位点造成了氨基酸极性或带电性的改变(F305S、T14A),CVA10样本则有9个(D25N、A33T、F148Y、Q223L、A291S、A78T、N27E、V240E、V107T)。以上结果提示当地需密切关注病毒流行谱和动态监测HFMD患者临床症状,以防病毒蛋白结构和功能的改变,加重其毒性和感染力。
基金supported by the National Science and Technology Major Project of China(No.2018ZX10201001-010,No.2017ZX10103009-005,No.2018ZX10713001-007)the National Natural Science Fund for Distinguished Young Scholars of China(No.81525023)+4 种基金the National Natural Science Foundation of China(No.81473031)the Program of Shanghai Academic/Technology Research Leader(No.18XD1400300)the Li Ka Shing Oxford Global Health Programme(No.B9RST00-B900.57)the Chinese Preventive Medicine Association(No:20101801)supported by CAS Pioneer Hundred Talents Program
文摘Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.
