Department of Neurology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
Int J Mol Sci. 2018 Mar 9;19(3):786. doi: 10.3390/ijms19030786.
The pathogenesis of multiple sclerosis (MS) has not been clarified. In addition to environmental factors; genetic determinants have been implicated in the pathogenesis of MS. Furthermore, endogenous retroviruses (ERV) might play a role in MS. The presence of oligoclonal immunoglobulin in cerebrospinal fluid (CSF) is a typical feature of MS. Recently, genetic polymorphisms in loci on human chromosomes 6, 14 and 18 have been identified as major determinants of CSF antibody levels in MS. The functional relevance of these single nucleotide polymorphisms (SNPs) remains unclear and none of them is located in an open reading frame. In previous studies, we identified ERV sequences in the vicinity of MS associated SNPs. Here, we describe the identification of ERV sequences in the neighborhood of SNPs associated with CSF antibody levels. All of the identified SNPs are located in the vicinity of ERV sequences. One of these sequences has very high homology to a sequence derived from the so-called MS-associated retrovirus (MSRV). Another cluster of three ERV sequences from the immunoglobulin heavy chain locus has retained the typical organization of retroviral genomes. These observations might shed new light on a possible association between ERVs and MS pathogenesis.
多发性硬化症（MS）的发病机制尚未阐明。除环境因素外；遗传决定因素也与 MS 的发病机制有关。此外，内源性逆转录病毒（ERV）可能在 MS 中发挥作用。脑脊液（CSF）中寡克隆免疫球蛋白的存在是 MS 的典型特征。最近，已确定人类染色体 6、14 和 18 上的基因座中的遗传多态性是 MS 中 CSF 抗体水平的主要决定因素。这些单核苷酸多态性（SNPs）的功能相关性尚不清楚，而且它们都不在开放阅读框中。在之前的研究中，我们在 MS 相关 SNP 附近鉴定出了 ERV 序列。在这里，我们描述了与 CSF 抗体水平相关 SNP 附近 ERV 序列的鉴定。所有鉴定的 SNP 都位于 ERV 序列附近。其中一个序列与所谓的与 MS 相关的逆转录病毒（MSRV）衍生的序列具有非常高的同源性。来自免疫球蛋白重链基因座的三个 ERV 序列簇保留了逆转录病毒基因组的典型组织。这些观察结果可能为 ERV 与 MS 发病机制之间的可能关联提供新的线索。
