Kassiotis George, Stoye Jonathan P
Retroviral Immunology, The Francis Crick Institute, London, UK
Department of Medicine, Faculty of Medicine, Imperial College London, London, UK.
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19;372(1732). doi: 10.1098/rstb.2016.0277.
Like all other mammals, humans harbour an astonishing number of endogenous retroviruses (ERVs), as well as other retroelements, embedded in their genome. These remnants of ancestral germline infection with distinct exogenous retroviruses display various degrees of open reading frame integrity and replication capability. Modern day exogenous retroviruses, as well as the infectious predecessors of ERVs, are demonstrably oncogenic. Further, replication-competent ERVs continue to cause cancers in many other species of mammal. Moreover, human cancers are characterized by transcriptional activation of human endogenous retroviruses (HERVs). These observations conspire to incriminate HERVs as causative agents of human cancer. However, exhaustive investigation of cancer genomes suggests that HERVs have entirely lost the ability for re-infection and thus the potential for insertional mutagenic activity. Although there may be non-insertional mechanisms by which HERVs contribute to cancer development, recent evidence also uncovers potent anti-tumour activities exerted by HERV replication intermediates or protein products. On balance, it appears that HERVs, despite their oncogenic past, now represent potential targets for immune-mediated anti-tumour mechanisms.This article is part of the themed issue 'Human oncogenic viruses'.
与所有其他哺乳动物一样，人类基因组中嵌入了数量惊人的内源性逆转录病毒（ERV）以及其他逆转录元件。这些源自不同外源性逆转录病毒的祖传种系感染残余物，呈现出不同程度的开放阅读框完整性和复制能力。现代的外源性逆转录病毒以及ERV的传染性前身，都具有明显的致癌性。此外，具有复制能力的ERV在许多其他哺乳动物物种中仍会引发癌症。而且，人类癌症的特征是人类内源性逆转录病毒（HERV）的转录激活。这些观察结果共同表明HERV是人类癌症的致病因素。然而，对癌症基因组的详尽研究表明，HERV已完全丧失了再次感染的能力，因此也失去了插入诱变活性的可能性。尽管HERV可能通过非插入机制促进癌症发展，但最近的证据也揭示了HERV复制中间体或蛋白质产物所发挥的强大抗肿瘤活性。总体而言，尽管HERV过去具有致癌性，但现在它们似乎是免疫介导抗肿瘤机制的潜在靶点。本文是主题为“人类致癌病毒”的特刊的一部分。
