抗内源性逆转录病毒的抗体
Antibodies against endogenous retroviruses
影响因子:8.30000
分区:医学2区 / 免疫学2区
发表日期:2024 Nov
作者:
Mihaela Chisca, Jean-David Larouche, Qi Xing, George Kassiotis
摘要
人类基因组具有数十万古代逆转录病毒的一体化，这些整合数百万年了。为了减少基因组的进一步扩增，宿主通过表观遗传抑制阻止这些现在的内源性逆转录病毒（ERV），并且随着进化时间，ERV被积累的突变和缺失无能力。然而，最近内生源ERV组的几个成员仍然保留产生病毒RNA，逆转录病毒蛋白和高阶结构（包括病毒体）的能力。病毒特征的保留，再加上表观抑制的可逆性，尤其是在癌症中看到的，可以使自适应免疫系统视为一种真正的逆转录病毒感染，从而可以对此进行免疫意外的ERV表达。因此，已经在不同的疾病中，有时在健康个体中检测到用ERV抗原反应作用的抗体。尽管它们是自我的一部分，但ERV抗原的逆转录病毒遗产以及与疾病状态的因果关系的关联并可能使它们与典型的自我抗原区分开来。因此，靶向ERV抗原的抗体的致病性或实际上是宿主保护能力可能是上下文依赖的。在这里，我们回顾了典型的ERV蛋白的免疫原性，重点是抗体反应及其潜在疾病的影响。
Abstract
The human genome harbors hundreds of thousands of integrations of ancient retroviruses, amassed over millions of years of evolution. To reduce further amplification in the genome, the host prevents transcription of these now endogenous retroviruses (ERVs) through epigenetic repression and, with evolutionary time, ERVs are incapacitated by accumulating mutations and deletions. However, several members of recently endogenized ERV groups still retain the capacity to produce viral RNA, retroviral proteins, and higher order structures, including virions. The retention of viral characteristics, combined with the reversible nature of epigenetic repression, particularly as seen in cancer, allow for immunologically unanticipated ERV expression, perceived by the adaptive immune system as a genuine retroviral infection, to which it has to respond. Accordingly, antibodies reactive with ERV antigens have been detected in diverse disorders and, occasionally, in healthy individuals. Although they are part of self, the retroviral legacy of ERV antigens, and association with and, possibly, causation of disease states may set them apart from typical self-antigens. Consequently, the pathogenic or, indeed, host-protective capacity of antibodies targeting ERV antigens is likely to be context-dependent. Here, we review the immunogenicity of typical ERV proteins, with emphasis on the antibody response and its potential disease implications.