Williams Ciğdem H, Oikarinen Sami, Tauriainen Sisko, Salminen Kimmo, Hyöty Heikki, Stanway Glyn
Department of Biological Sciences, Central Campus, University of Essex, Colchester, CO4 3SQ, United Kingdom.
J Clin Microbiol. 2006 Feb;44(2):441-8. doi: 10.1128/JCM.44.2.441-448.2006.
Growing evidence has implicated members of the genus Enterovirus of the family Picornaviridae in the etiology of some cases of type 1 diabetes (T1D). To contribute to an understanding of the molecular determinants underlying this association, we determined the complete nucleotide sequence of a strain of echovirus 3 (E3), Human enterovirus B (HEV-B) species, isolated from an individual who soon after virus isolation developed autoantibodies characteristic of T1D. The individual has remained positive for over 6 years for tyrosine phosphatase-related IA-2 protein autoantibodies and islet cell autoantibodies, indicating an ongoing autoimmune process, although he has not yet developed clinical T1D. The sequence obtained adds weight to the observation that recent enterovirus isolates differ significantly from prototype strains and provides further evidence of a role for recombination in enterovirus evolution. In common with most HEV-B species members, the isolate exhibits 2C and VP1 sequences suggested as triggers of autoimmunity through molecular mimicry. However, comparisons with the E3 prototype strain and previously reported diabetogenic and nondiabetogenic HEV-B strains do not reveal clear candidates for sequence features of PicoBank/DM1/E3 that could be associated with autoantibody appearance. This is the first time a virus strain isolated at the time of commencement of beta-cell damage has been analyzed and is an invaluable addition to enterovirus strains isolated previously at the onset of T1D in the search for specific molecular features which could be associated with diabetes induction.
越来越多的证据表明，小核糖核酸病毒科肠道病毒属的成员与某些1型糖尿病（T1D）病例的病因有关。为了有助于理解这种关联背后的分子决定因素，我们测定了从一名个体分离出的一种埃可病毒3（E3）毒株的完整核苷酸序列，该毒株属于人肠道病毒B（HEV-B）种，该个体在病毒分离后不久就产生了T1D特征性的自身抗体。该个体酪氨酸磷酸酶相关IA-2蛋白自身抗体和胰岛细胞自身抗体6年多来一直呈阳性，表明自身免疫过程持续存在，尽管他尚未发展为临床T1D。获得的序列进一步证明了最近分离的肠道病毒与原型毒株有显著差异，并为重组在肠道病毒进化中的作用提供了进一步证据。与大多数HEV-B种成员一样，该分离株的2C和VP1序列被认为是通过分子模拟引发自身免疫的因素。然而，与E3原型毒株以及先前报道的致糖尿病和非致糖尿病的HEV-B毒株进行比较，并未发现PicoBank/DM1/E3序列特征中可能与自身抗体出现相关的明确候选因素。这是首次对在β细胞损伤开始时分离出的病毒毒株进行分析，对于先前在T1D发病时分离出的肠道病毒毒株而言，这是一项宝贵的补充，有助于寻找可能与糖尿病诱导相关的特定分子特征。
