了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分...了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分析。使用RD细胞进行病毒分离,RT-PCR扩增CV-A10的VP1区基因片段并进行序列测定,使用Meg Align软件进行核苷酸及氨基酸的同源性分析,并使用MEGA5.0软件构建系统进化树。2014年CV-A10是陕西HFMD病原谱中的第三大病原,占其他肠道病毒的57.71%,13例重症HFMD病例的致病病原体鉴定为CV-A10,占重症病例的9.03%。CV-A10感染HFMD病例以≤3岁年龄组儿童为主(83.07%),男女性别比为1.15∶1。发病时间主要集中在4~7月。实验室分离出101株CV-A10,覆盖全省10市(区)。完成测序的18株CV-A10核苷酸和氨基酸同源性分别为94.0%~100.0%和97.3%~100.0%,与A型原型株的核苷酸和氨基酸同源性分别为76.2%~77.5%和91.9%~93.0%,与近年来河北、湖南和河南地区流行株具有较高的同源性。系统进化显示陕西CV-A10分离株属于C基因型。CV-A10是2014年陕西HFMD的优势病原,能引起重症HFMD,本次分离到的CV-A10毒株均属于C基因型。展开更多
Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particu...Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particularly young children,may have different immunological responses to infection.Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus.The characteristics of CV-A10 infection,replication,and shedding in humans remain unknown.In this study,rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans.The clinical symptoms,viral shedding,inflammatory response and pathologic changes were investigated in acute infection(1–11 day post infection)and recovery period(12–180 day post infection).All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans.Substantial inflammatory pathological damages were observed in multi-organs,including the lung,heart,liver,and kidney.During the acute period,all rhesus macaques displayed clinical signs,viral shedding,normalization of serum cytokines,and increased serum neutralizing antibodies,whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period.In addition,there were no significant differences between respiratory and digestive tract infected animals.Overall,all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.展开更多
文摘了解陕西省手足口病(Hand,foot and mouth disease,HFMD)的致病病原体柯萨奇病毒A10型(CV-A10)的流行特征及VP1区基因特征。对2014年收集的HFMD病例标本,通过荧光定量PCR检测确定肠道病毒型别,对CV-A10引起的HFMD流行特征进行描述性分析。使用RD细胞进行病毒分离,RT-PCR扩增CV-A10的VP1区基因片段并进行序列测定,使用Meg Align软件进行核苷酸及氨基酸的同源性分析,并使用MEGA5.0软件构建系统进化树。2014年CV-A10是陕西HFMD病原谱中的第三大病原,占其他肠道病毒的57.71%,13例重症HFMD病例的致病病原体鉴定为CV-A10,占重症病例的9.03%。CV-A10感染HFMD病例以≤3岁年龄组儿童为主(83.07%),男女性别比为1.15∶1。发病时间主要集中在4~7月。实验室分离出101株CV-A10,覆盖全省10市(区)。完成测序的18株CV-A10核苷酸和氨基酸同源性分别为94.0%~100.0%和97.3%~100.0%,与A型原型株的核苷酸和氨基酸同源性分别为76.2%~77.5%和91.9%~93.0%,与近年来河北、湖南和河南地区流行株具有较高的同源性。系统进化显示陕西CV-A10分离株属于C基因型。CV-A10是2014年陕西HFMD的优势病原,能引起重症HFMD,本次分离到的CV-A10毒株均属于C基因型。
基金the Medical and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences(CIFMS,2016-I2M-2-001)National Resource Center for Non-Human Primates,Major Science and Technology Special Projects in Yunnan ProvinceKunming Science and Technology Innovation and Service Capacity Enhancement Program Key Projects(2016-2-R-07674)。
文摘Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particularly young children,may have different immunological responses to infection.Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus.The characteristics of CV-A10 infection,replication,and shedding in humans remain unknown.In this study,rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans.The clinical symptoms,viral shedding,inflammatory response and pathologic changes were investigated in acute infection(1–11 day post infection)and recovery period(12–180 day post infection).All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans.Substantial inflammatory pathological damages were observed in multi-organs,including the lung,heart,liver,and kidney.During the acute period,all rhesus macaques displayed clinical signs,viral shedding,normalization of serum cytokines,and increased serum neutralizing antibodies,whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period.In addition,there were no significant differences between respiratory and digestive tract infected animals.Overall,all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.