针对内源性逆转录病毒的抗体
Antibodies against endogenous retroviruses
DOI 原文链接
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影响因子:8.3
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
DOI:
10.1111/imr.13378
摘要
人类基因组中携带数十万份古老逆转录病毒的整合序列，这些病毒在数百万年的进化过程中逐渐积累。为了防止这些逆转录病毒在基因组中的进一步扩增，宿主通过表观遗传抑制机制阻止其转录，随着时间推移，逆转录病毒逐渐因突变和缺失而失去活性。然而，近期内源化逆转录病毒群的若干成员仍保留产生病毒RNA、逆转录病毒蛋白及高阶结构（包括病毒粒子）的能力。病毒特性的保留，加之表观遗传抑制的可逆性，特别是在癌症中，可能引发免疫系统意想不到的逆转录病毒表达，被适应性免疫系统误认为是真实的逆转录病毒感染，从而引发免疫反应。相应地，在多种疾病中，甚至健康个体中，都已检测到对逆转录病毒抗原具有反应的抗体。尽管它们是机体自身的一部分，但逆转录病毒遗产中的逆转录病毒抗原及其与疾病状态的关联，甚至可能的因果关系，将它们与典型的自身抗原区分开来。因此，针对逆转录病毒抗原的抗体的致病性或宿主保护作用，可能具有一定的依赖于具体环境的特性。本文综述了典型逆转录病毒蛋白的免疫原性，重点关注抗体反应及其潜在的疾病意义。
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.