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通过计算机模拟研究柯萨奇病毒B4 VP4衣壳蛋白的特异性。

Specificity of the coxsackievirus B4 VP4 capsid protein investigated in silico.

作者信息

Goffard Anne, Sané Famara, Soumillon Magali, Hober Didier

机构信息

College of Pharmacy, Université Lille Nord de France, Lille Cedex, France.

出版信息

Discov Med. 2011 Aug;12(63):153-8.

Abstract

The Enterovirus genus encompasses several species and various serotypes, like coxsackievirus-B1 (CV-B1) to CV-B6, and many variants. The role of these viruses, especially CV-B4, in the pathogenesis of type 1 diabetes is strongly suspected. It has been reported that antibodies directed towards the region of amino acids 11-30 of the VP4 capsid protein enhance the infection of human peripheral blood mononuclear cells with CV-B4. In order to predict the inter- and intra-serotype specificity of the region 11-30 of CV-B4 VP4, 362 available protein sequences of CV-B1 to -B6, CV-A9, and swine vesicular disease virus (SVDV) have been aligned and levels of homology have been calculated. Serine residue substitutions in this region of VP4 were observed without predictable subsequent modification of conformation or charge. The amino acids 16-24 region was the most variable. The sequence of amino acids 16-24 of the CV-B4E2 VP4 protein was highly homologous to those of other CV-B4 (64.4%) whereas there was no homology with CV-B3 and B5 and very low levels of homology with CV-B1 and B2 (3.3% and 9.9%, respectively). In conclusion, the bioinformatic analysis suggests that the region 16-24 of the VP4 capsid protein is the feature of the specificity of the target of infection-enhancing antibodies directed towards CV-B.

摘要

肠道病毒属包含多个种和多种血清型,如柯萨奇病毒B1(CV-B1)至CV-B6以及许多变种。人们强烈怀疑这些病毒,尤其是CV-B4,在1型糖尿病发病机制中的作用。据报道,针对VP4衣壳蛋白氨基酸11 - 30区域的抗体可增强CV-B4对人外周血单个核细胞的感染。为了预测CV-B4 VP4蛋白11 - 30区域的血清型间和血清型内特异性,已对CV-B1至-B6、CV-A9和猪水疱病病毒(SVDV)的362个可用蛋白序列进行了比对,并计算了同源性水平。在VP4的该区域观察到丝氨酸残基替换,且未发现构象或电荷有可预测的后续改变。氨基酸16 - 24区域变化最大。CV-B4E2 VP4蛋白的氨基酸16 - 24序列与其他CV-B4的序列高度同源(64.4%),而与CV-B3和B5无同源性,与CV-B1和B2的同源性水平极低(分别为3.3%和9.9%)。总之,生物信息学分析表明,VP4衣壳蛋白的16 - 24区域是针对CV-B的感染增强抗体靶标的特异性特征。

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