Al-Hello Haider, Paananen Anja, Eskelinen Mervi, Ylipaasto Petri, Hovi Tapani, Salmela K, Lukashev Alexander N, Bobegamage Shubhada, Roivainen Merja
Enterovirus Laboratory, National Public Health Institute, Helsinki, Finland.
Renal Transplant Unit, Helsinki University Hospital, Helsinki, Finland.
J Gen Virol. 2008 Aug;89(Pt 8):1949-1959. doi: 10.1099/vir.0.83474-0.
An enterovirus strain (designated D207) isolated from a Slovakian diabetic child and originally serotyped as coxsackievirus A9 (CAV-9) was found to cause rapid cytolysis coinciding with severe functional damage of the surviving cells in primary cultures of human pancreatic islets. This finding prompted us to clone the isolate for full-length genome sequencing and molecular characterization as the prototype strain of CAV-9 is known to cause only minimal damage to insulin-producing beta-cells. Based on capsid-coding sequence comparisons, the isolate turned out to be echovirus 11 (E-11). Phylogenetic analyses demonstrated that E-11/D207 was closely related to a specific subgroup B of E-11 strains known to cause uveitis. To study further antigenic properties of isolate E-11/D207 and uveitis-causing E-11 strains, neutralization experiments were carried out with CAV-9- and E-11-specific antisera. Unlike the prototype strains, the isolate E-11/D207 and uveitis-causing E-11 strains were well neutralized with both CAV-9- and E-11-specific antisera. Attempts to identify recombination of the capsid coding sequences as a reason for double-reactivity using the Simplot analysis failed to reveal major transferred motifs. However, peptide scanning technique was able to identify antigenic regions of capsid proteins of E-11/D207 as well as regions cross-reacting with an antiserum raised to CAV-9. Thus, double specificity of E-11/D207 seems to be a real characteristic shared by the phylogenetically closely related virus strains in the genetic subgroup B of E-11.
从一名斯洛伐克糖尿病儿童分离出的一种肠道病毒毒株(命名为D207),最初血清型鉴定为柯萨奇病毒A9(CAV-9),结果发现它能在人胰岛原代培养物中引起快速细胞溶解,同时伴有存活细胞的严重功能损伤。这一发现促使我们对该分离株进行克隆,以进行全长基因组测序和分子特征分析,因为已知CAV-9的原型毒株对产生胰岛素的β细胞仅造成极小损伤。基于衣壳编码序列比较,该分离株结果显示为艾柯病毒11型(E-11)。系统发育分析表明,E-11/D207与已知可引起葡萄膜炎的E-11毒株的特定B亚组密切相关。为了进一步研究分离株E-11/D207和引起葡萄膜炎的E-11毒株的抗原特性,用CAV-9和E-11特异性抗血清进行了中和实验。与原型毒株不同,分离株E-11/D207和引起葡萄膜炎的E-11毒株都能被CAV-9和E-11特异性抗血清有效中和。试图通过Simplot分析确定衣壳编码序列的重组是双重反应性的原因,但未发现主要的转移基序。然而,肽扫描技术能够鉴定出E-11/D207衣壳蛋白的抗原区域以及与针对CAV-9产生的抗血清发生交叉反应的区域。因此,E-11/D207的双重特异性似乎是E-11遗传亚组B中系统发育密切相关的病毒毒株共有的一个真实特征。