How Retroviruses and Retrotransposons in Our Genome May Contribute to Autoimmunity in Rheumatological Conditions.
How Retroviruses and Retrotransposons in Our Genome May Contribute to Autoimmunity in Rheumatological Conditions.
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DOI：
10.3389/fimmu.2020.593891
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发表时间：
2020
影响因子：
7.3
通讯作者：
Ukadike KC
中科院分区：
文献类型：
--
作者：
Mustelin T;Ukadike KC
超过200种人类疾病包括自身免疫的各种表现。导致这些疾病的分子事件仍然不完全清楚，其原因在很大程度上仍然未知。多年来，已经提出了许多自身免疫的潜在触发因素，但其中很少有人得到最终证实或坚决反驳。几十年来，病毒一直是最受怀疑的病毒，似乎许多病毒，包括疱疹病毒科的病毒，确实可以通过许多机制影响疾病的发生和/或促进疾病的恶化，这些机制包括延长的抗病毒免疫力、免疫破坏因子和机制，以及可能的“分子模拟”。然而，目前还没有一种特定的病毒被确定为真正的病因。在这里，我们讨论了一种不同的，但可能是机械相关的可能性，即过去感染我们并在我们的基因组中留下持久拷贝的逆转录转座子或逆转录病毒仍然可以引起导致自身免疫性疾病的不断升级的免疫反应。这些基因座中的许多仍然编码保留了部分或全部原始功能的逆转录病毒蛋白。重要的是，这些内源性前病毒不能被免疫系统消除，就像它可以消除外源性病毒一样。因此，如果不加以适当控制，它们可能会导致慢性或偶发性免疫反应受挫并逐步升级，最终导致明显的自身免疫性疾病。在这里，我们讨论了证据和提出的机制，并评估了从目前对这一领域的理解中出现的治疗方案。
More than 200 human disorders include various manifestations of autoimmunity. The molecular events that lead to these diseases are still incompletely understood and their causes remain largely unknown. Numerous potential triggers of autoimmunity have been proposed over the years, but very few of them have been conclusively confirmed or firmly refuted. Viruses have topped the lists of suspects for decades, and it seems that many viruses, including those of the Herpesviridae family, indeed can influence disease initiation and/or promote exacerbations by a number of mechanisms that include prolonged anti-viral immunity, immune subverting factors, and mechanisms, and perhaps “molecular mimicry”. However, no specific virus has yet been established as being truly causative. Here, we discuss a different, but perhaps mechanistically related possibility, namely that retrotransposons or retroviruses that infected us in the past and left a lasting copy of themselves in our genome still can provoke an escalating immune response that leads to autoimmune disease. Many of these loci still encode for retroviral proteins that have retained some, or all, of their original functions. Importantly, these endogenous proviruses cannot be eliminated by the immune system the way it can eliminate exogenous viruses. Hence, if not properly controlled, they may drive a frustrated and escalating chronic, or episodic, immune response to the point of a frank autoimmune disorder. Here, we discuss the evidence and the proposed mechanisms, and assess the therapeutic options that emerge from the current understanding of this field.
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影响因子：
3.3
作者：
Arjan-Odedra S;Swanson CM;Sherer NM;Wolinsky SM;Malim MH
通讯作者：
Malim MH
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
13.3
作者：
An, Jie;Durcan, Laura;Elkon, Keith B.
通讯作者：
Elkon, Keith B.
影响因子：
5.4
作者：
Bashratyan, Roman;Regn, Danielle;Dai, Yang D.
通讯作者：
Dai, Yang D.
影响因子：
5.4
作者：
Bhardwaj, Neeru;Maldarelli, Frank;Coffin, John M.
通讯作者：
Coffin, John M.