Abstract
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.
Highlights
About half of the human genome is composed of transposable elements (TEs) [1,2]
After a brief introduction on Human Endogenous Retroviruses (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
This shared property between exogenous and endogenous retroviruses led to the identification of an immunosuppressive domain (ISD) in the transmembrane unit of the Env protein
Summary
About half of the human genome is composed of transposable elements (TEs) [1,2]. Initially considered as “junk DNA”, these mobile sequences have been shown to provide a major source of structural variation in the genome with an impact on oncogenesis [1]. HERVs complete structure is the same as that of exogenous retroviruses, consisting of four genes (gag, pro, pol and env) flanked by two long-terminal repeats (LTRs) (Figure 1A) [3]. These LTRs function as promoters for HERV expression, have strong RNA regulatory sequences and contain transcription factor binding sites. 2, two HERV-W/HERV-FRD derived envelope expressed in the placenta playing a role in trophoblast formation and foeto-maternal tolerance [6]. The mechanisms and targets of Env-mediated fully defined, and its role cancer immune escape notrole clearly established. Clearly replication intermediates can stimulate innate sensors promoting antitumoral immune response by established. Discuss the interactions between HERVs and the innate immune response, before considering the implication of HERVs expression in the antitumor immune response
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