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Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers

机译:人类内源性逆转录病毒(HERV):塑造癌症的先天免疫反应。

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摘要

Human Endogenous Retroviruses (HERVs) are accounting for 8% of the human genome. These sequences are remnants from ancient germline infections by exogenous retroviruses. After million years of evolution and multiple integrations, HERVs have acquired many damages rendering them defective. At steady state, HERVs are mostly localized in the heterochromatin and silenced by methylation. Multiple conditions have been described to induce their reactivation, including auto-immune diseases and cancers. HERVs re-expression leads to RNA (simple and double-stranded) and DNA production (by reverse transcription), modulating the innate immune response. Some studies also argue for a role of HERVs in shaping the evolution of innate immunity, notably in the development of the interferon response. However, their exact role in the innate immune response, particularly in cancer, remains to be defined. In this review, we see how HERVs could be key-players in mounting an antitumor immune response. After a brief introduction on HERVs characteristics and biology, we review the different mechanisms by which HERVs can interact with the immune system, with a focus on the innate response. We then discuss the potential impact of HERVs expression on the innate immune response in cancer.
机译:人类内源性逆转录病毒(HERV)占人类基因组的8%。这些序列是来自外源逆转录病毒的古老种系感染的残留。经过数百万年的发展和多次集成,HERV遭受了许多损害,使其成为有缺陷的。在稳定状态下,HERV主要位于异染色质中,并通过甲基化沉默。已经描述了多种条件来诱导它们的活化,包括自身免疫性疾病和癌症。 HERV的重新表达导致RNA(简单和双链)和DNA产生(通过逆转录),从而调节先天免疫应答。一些研究还指出,HERVs在影响先天免疫进化,特别是在干扰素应答发展中的作用。然而,它们在先天免疫应答中,特别是在癌症中的确切作用还有待确定。在这篇综述中,我们看到了HERV如何成为引发抗肿瘤免疫反应的关键因素。在简要介绍了HERV的特性和生物学特性之后,我们重点介绍了HERV与免疫系统相互作用的不同机制。然后,我们讨论了HERVs表达对癌症固有免疫反应的潜在影响。

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