Emerging roles for endogenous retroviruses in immune epigenetic regulation*

Buttler, Carmen A; Chuong, Edward B.

doi:10.1111/imr.13042

Cited by 26 publications

(19 citation statements)

References 173 publications

(187 reference statements)

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“…So, the presentation of HERV `self-antigens` can favor the T and B cells to become immunologically aware of the existence of endogenous retroelements, and maybe avoid the development of some diseases, mainly autoimmune diseases. However, it was also reported that the host responses to several types of infectious agents, by increasing the transcriptional induction of endogenous retroelements, can rise the responses of T cells and B cells for these retroelements ( 78 , 79 ).…”

Section: Factors That Contribute For Hervs Expressionmentioning

confidence: 99%

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

Rangel

Silva

et al. 2022

Front. Immunol.

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Human Endogenous Retroviruses (HERVs) are derived from ancient exogenous retroviral infections that have infected our ancestors’ germline cells, underwent endogenization process, and were passed throughout the generations by retrotransposition and hereditary transmission. HERVs comprise 8% of the human genome and are critical for several physiological activities. Yet, HERVs reactivation is involved in pathological process as cancer and autoimmune diseases. In this review, we summarize the multiple aspects of HERVs’ role within the human genome, as well as virological and molecular aspects, and their fusogenic property. We also discuss possibilities of how the HERVs are possibly transactivated and participate in modulating the inflammatory response in health conditions. An update on their role in several autoimmune, inflammatory, and aging-related diseases is also presented.

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Section: Factors That Contribute For Hervs Expressionmentioning

confidence: 99%

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

Rangel

Silva

et al. 2022

Front. Immunol.

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“…Collectively, the presence of HERVs in cCREs that are based in experimental data, suggest that HERV sequences may impact, in different degree, the epigenetic regulation of 4 out 5 human genes. The fact that HERVs contain an abundance of regulatory elements [ 66 , 67 , 68 ] and are actively transcribed in humans [ 69 ] strengthen the possible impact of the above finding. It should be noted that the regulatory potential of HERVs sequences may also involve viral transcription factors.…”

Section: Discussionmentioning

confidence: 98%

A Systems Biology Approach on the Regulatory Footprint of Human Endogenous Retroviruses (HERVs)

Μαρκόπουλος

2022

Diseases

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Human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that comprise the ~8.93% of the human genome sequence, with a high proportion being human specific. The recent expansion of repeated HERV sequences has offered a framework for genetic and epigenetic innovation. In the current report, a systematic approach is implemented to catalogue regulatory elements within HERVs, as a roadmap to potential functions of HERV sequences in gene networks. ENCODE Project has offered a wealth of epigenetic data based on omics technologies. I analyzed the presence of HERV sequences on consensus cis-regulatory elements (cCREs) from ENCODE data. On the one side, HERVs are in 1 out of 9 cCREs (>100.000 cCREs in total), dispersed within the genome and present in cis-regulatory regions of ~81% of human genes, as calculated following gene enrichment analysis. On the other side, promoter-associated HERV cCREs are present adjacent to (in a 200 bp window) the transcription start sites of 256 human genes. Regulatory network production, followed by centrality analysis led to the discovery of 90 core genes containing HERV-associated promoters. Pathway analysis on the core network genes and their immediate neighbors revealed a regulatory footprint that, among others, is associated with inflammation, chemokine signaling and response to viral infection. Collectively, these results support the concept that the expansion of regulatory sequences derived from HERVs is critical for epigenetic innovation that may have wired together genes into novel transcriptional networks with critical roles in cellular physiology and pathology.

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“…Transposable elements (TEs), which occupy half of the human genome, play critical roles as cis-regulatory elements in various human biological processes (Bourque, 2009; Bourque et al, 2018; Chuong et al, 2017). Notably, a particular subclass of TEs, Endogenous Retroviruses (ERVs), are derived from ancient retrovirus, suggesting a potential association with infection and immunity (Buttler and Chuong, 2021; Kassiotis and Stoye, 2016; Srinivasachar Badarinarayan and Sauter, 2021). Confirming this, an ERV family, MER41, was found to be co-opted as cis-regulatory elements in the primate innate immune response (Bogdan et al, 2020; Chuong et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Transposable elements are associated with the variable response to influenza infection

Chen

Pacis

Aracena

et al. 2022

Preprint

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SUMMARYInfluenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Given that transposable elements (TEs) contribute to the activation of innate immunity, we wanted to explore their potential role in this variability. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection. Using ATAC-seq we identified a set of TE families with either enhanced or reduced accessibility upon infection. Of the enhanced families, 15 showed high variability between individuals and had distinct epigenetic profiles. Motif analysis showed an association with known immune regulators in stably enriched TE families and with other factors in variable families, including KRAB-ZNFs. We also observed a strong association between basal TE transcripts and viral load post infection. Finally, we built a predictive model suggesting that TEs, and host factors regulating TEs, contribute to the variable response to infection.

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Emerging roles for endogenous retroviruses in immune epigenetic regulation*

Cited by 26 publications

References 173 publications

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

A Systems Biology Approach on the Regulatory Footprint of Human Endogenous Retroviruses (HERVs)

Transposable elements are associated with the variable response to influenza infection

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