Chisca Mihaela, Larouche Jean-David, Xing Qi, Kassiotis George
Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.
Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.
Immunol Rev. 2024 Nov;328(1):300-313. doi: 10.1111/imr.13378. Epub 2024 Aug 17.
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.
人类基因组中存在着数十万种古代逆转录病毒的整合序列，这些序列是在数百万年的进化过程中积累下来的。为了减少基因组中的进一步扩增，宿主通过表观遗传抑制来阻止这些现已内源性逆转录病毒（ERVs）的转录，并且随着时间的推移，ERVs会因积累突变和缺失而失去活性。然而，最近内源性ERV群体中的几个成员仍然保留产生病毒RNA、逆转录病毒蛋白和包括病毒粒子在内的高级结构的能力。病毒特征的保留，加上表观遗传抑制的可逆性，特别是在癌症中所见的情况，使得适应性免疫系统将其视为真正的逆转录病毒感染而产生免疫上意想不到的ERV表达，并必须对此做出反应。因此，在各种疾病中，甚至偶尔在健康个体中，都检测到了与ERV抗原反应的抗体。尽管ERV抗原是自身的一部分，但它们的逆转录病毒遗传特性以及与疾病状态的关联甚至可能的因果关系可能使它们有别于典型的自身抗原。因此，靶向ERV抗原的抗体的致病能力或实际上的宿主保护能力可能取决于具体情况。在这里，我们综述了典型ERV蛋白的免疫原性，重点是抗体反应及其对疾病的潜在影响。
