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内源性逆转录病毒与多发性硬化症——谜题的新线索。

Endogenous retroviruses and multiple sclerosis-new pieces to the puzzle.

机构信息

Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000, Aarhus, C, Denmark.

出版信息

BMC Neurol. 2013 Aug 28;13:111. doi: 10.1186/1471-2377-13-111.

Abstract

The possibility that retroviruses play a role in multiple sclerosis (MS) has long been considered; accumulating findings suggest this to be most likely in the form of human endogenous retroviruses (HERVs). A genetic test series of fifty endogenous retroviral loci for association with MS in Danes showed SNP markers near a specific endogenous retroviral locus, HERV-Fc1 located on the X-chromosome, to be positive. Bout Onset MS was associated with the HERV-Fc1 locus, while a rarer form, Primary Progressive MS, was not. Moreover, HERV-Fc1 Gag RNA in plasma was increased 4-fold in patients with recent history of attacks, relative to patients in a stable state and to healthy controls.Finally, genetic variations in restriction genes for retroviruses influence the risk of MS, providing further support for a role of retroviral elements in disease.We speculate that endogenous retroviruses may activate the innate immune system in a variety of ways, involving the host proteins, TRIMs, TLRs, TREXs and STING. Observations in HIV-positive patients suggest that antiretroviral drugs can curb MS. Thus, these new findings regarding the etiology and pathogenesis of MS, suggest alternative ways to challenge autoimmune diseases.

摘要

逆转录病毒在多发性硬化症(MS)中的作用一直备受关注;越来越多的研究结果表明,人类内源性逆转录病毒(HERV)最有可能发挥作用。在丹麦进行的一项针对五十个内源性逆转录病毒基因座与 MS 相关性的基因测试系列研究显示,X 染色体上特定内源性逆转录病毒基因座 HERV-Fc1 附近的 SNP 标记呈阳性。Bout Onset MS 与 HERV-Fc1 基因座相关,而一种更为罕见的形式原发性进行性 MS 则不相关。此外,与处于稳定状态的患者和健康对照者相比,近期有发作史的患者血浆中的 HERV-Fc1 Gag RNA 增加了 4 倍。最后,限制逆转录病毒的基因的遗传变异影响 MS 的风险,为逆转录病毒在疾病中的作用提供了进一步的支持。我们推测内源性逆转录病毒可能通过多种方式激活先天免疫系统,涉及宿主蛋白 TRIMs、TLRs、TREXs 和 STING。在 HIV 阳性患者中的观察结果表明,抗逆转录病毒药物可以抑制 MS。因此,这些关于 MS 病因和发病机制的新发现,为挑战自身免疫性疾病提供了新的途径。

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