scholarly journals The Roles of Human Endogenous Retroviruses (HERVs) in Inflammation

2021 ◽  
Vol 36 (2) ◽  
pp. 69-78
Author(s):  
Eun-Ji Ko ◽  
Hee-Jae Cha
Keyword(s):  
Inflammatory Response ◽  
Autoimmune Diseases ◽  
Molecular Level ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Action Mechanisms ◽  
Signaling Mechanisms ◽  
Lateral Sclerosis

Human endogenous retroviruses (HERVs) are ancient, currently inactive, and non-infectious due to recombination, deletions, and mutations in the host genome. However, HERV-derived elements are involved in physiological phenomena including inflammatory response. In recent studies, HERV-derived elements were involved directly in various inflammatory diseases including autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Sjogren’s syndrome. Regarding the involvement of HERV-derived elements in inflammation, two possible mechanisms have been proposed. First, HERV-derived elements cause nonspecific innate immune processes. Second, HERV-derived RNA or proteins might stimulate selective signaling mechanisms. However, it is unknown how silent HERV elements are activated in the inflammatory response and what factors and signaling mechanisms are involved with HERV-derived elements. In this review, we introduce HERV-related autoimmune diseases and propose the possible action mechanisms of HERV-derived elements in the inflammatory response at the molecular level.

scholarly journals Extracellular Vesicles Released by Colorectal Cancer Cell Lines Modulate Innate Immune Response in Zebrafish Model: The Possible Role of Human Endogenous Retroviruses

2019 ◽  
Vol 20 (15) ◽  
pp. 3669 ◽  
Author(s):  
Luca Ferrari ◽  
Marco Cafora ◽  
Federica Rota ◽  
Mirjam Hoxha ◽  
Simona Iodice ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Cell Lines ◽  
Cancer Cell ◽  
Innate Immune Response ◽  
Colorectal Adenocarcinoma ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Colorectal Cancer Cell Lines

Extracellular vesicles (EVs) are important components of the metastatic niche and are crucial in infiltration, metastasis, and immune tolerance processes during tumorigenesis. We hypothesized that human endogenous retroviruses (HERV) positive EVs derived from tumor cellsmay have a role in modulating the innate immune response. The study was conducted in two different colorectal cancer cell lines, representing different stages of cancer development: Caco-2, derived from a non-metastatic colorectal adenocarcinoma, and SK-CO-1, derived from metastatic colorectal adenocarcinoma (ascites). Both cell lines were treated with decitabine to induce global hypomethylation and to reactivate HERV expression. EVs were quantified by nanoparticle tracking analysis, and HERV-positive EV concentrations were measured by flow cytometry. The effect of EVs isolated from both untreated and decitabine-treated cells on the innate immune response was evaluated by injecting them in zebrafish embryos and then assessing Interleukin 1β (IL1-β), Interleukin 10 (IL-10), and the myeloperoxidase (mpx) expression levels by real-time qPCR. Interestingly, HERV-K positive EVs concentrations were significantly associated with a reduced expression of IL1-β and mpx, supporting our hypothesis that HERV-positive EVs may act as immunomodulators in tumor progression. The obtained results open new perspectives about the modulation of the immune response in cancer therapy.

scholarly journals Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Cristina Municio ◽  
Gabriel Criado
Keyword(s):  
Autoimmune Diseases ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Epigenetic Reprogramming ◽  
Innate Immune Cells ◽  
Tissue Destruction ◽  
Specific Stimulus ◽  
Trained Immunity

The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.

scholarly journals Formation of HERV-K and HERV-Fc1 Envelope Family Members is Suppressed on Transcriptional and Translational Level

2020 ◽  
Vol 21 (21) ◽  
pp. 7855
Author(s):  
Victoria Gröger ◽  
Lisa Wieland ◽  
Marcel Naumann ◽  
Ann-Christin Meinecke ◽  
Beate Meinhardt ◽  
...  
Keyword(s):  
Cell Lines ◽  
Inflammatory Diseases ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Extrinsic Factors ◽  
Human Endogenous Retroviruses ◽  
Mammalian Cell Lines ◽  
Translational Level

The human genome comprises 8% sequences of retroviral origin, so-called human endogenous retroviruses (HERVs). Most of these proviral sequences are defective, but some possess open reading frames. They can lead to the formation of viral transcripts, when activated by intrinsic and extrinsic factors. HERVs are thought to play a pathological role in inflammatory diseases and cancer. Since the consequences of activated proviral sequences in the human body are largely unexplored, selected envelope proteins of human endogenous retroviruses associated with inflammatory diseases, namely HERV-K18, HERV-K113, and HERV-Fc1, were investigated in the present study. A formation of glycosylated envelope proteins was demonstrated in different mammalian cell lines. Nevertheless, protein maturation seemed to be incomplete as no transport to the plasma membrane was observed. Instead, the proteins remained in the ER where they induced the expression of genes involved in unfolded protein response, such as HSPA5 and sXBP1. Furthermore, low expression levels of native envelope proteins were increased by codon optimization. Cell-free expression systems showed that both the transcriptional and translational level is affected. By generating different codon-optimized variants of HERV-K113 envelope, the influence of single rare t-RNA pools in certain cell lines was demonstrated. The mRNA secondary structure also appears to play an important role in the translation of the tested viral envelope proteins. In summary, the formation of certain HERV proteins is basically possible. However, their complete maturation and thus full biologic activity seems to depend on additional factors that might be disease-specific and await elucidation in the future.

scholarly journals Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

2015 ◽  
Vol 64 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Bjørn A. Nexø ◽  
Palle Villesen ◽  
Kari K. Nissen ◽  
Hanne M. Lindegaard ◽  
Peter Rossing ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses

scholarly journals Endogenous Retroviruses in Nervous System Disorders

2021 ◽  
Vol 14 (1) ◽  
pp. 70
Author(s):  
Victoria Gröger ◽  
Alexander Emmer ◽  
Martin Staege ◽  
Holger Cynis
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Small Molecules ◽  
Treatment Strategies ◽  
Endogenous Retroviruses ◽  
Therapeutic Antibodies ◽  
Human Endogenous Retroviruses ◽  
New Treatment ◽  
Lateral Sclerosis

Human endogenous retroviruses (HERV) have been implicated in the pathogenesis of several nervous system disorders including multiple sclerosis and amyotrophic lateral sclerosis. The toxicity of HERV-derived RNAs and proteins for neuronal cells has been demonstrated. The involvement of HERV in the pathogenesis of currently incurable diseases might offer new treatment strategies based on the inhibition of HERV activities by small molecules or therapeutic antibodies.

cGAS-STING-mediated IFN-I response in host defense and neuro-inflammatory diseases

2021 ◽  
Vol 19 ◽  
Author(s):  
Kai Chen ◽  
Chuan Lai ◽  
Yin Su ◽  
Wen Dai Bao ◽  
Liu Nan Yang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Danger Signal ◽  
Downstream Signaling ◽  
Pathway Activation ◽  
Sting Pathway ◽  
Lateral Sclerosis

: The presence of foreign or misplaced nucleic acids is a danger signal that triggers innate immune responses through activating cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and binding to its downstream signaling effector stimulator of interferon genes (STING). Then the cGAS–STING pathway activation links nucleic acid sensing to immune responses and pathogenic entities clearance. However, overactivation of this signaling pathway leads to fatal immune disorders and contributes to the progression of many human inflammatory diseases. Therefore, optimal activation of this pathway is crucial for the elimination of invading pathogens and the maintenance of immune homeostasis. In this review, we will summarize its fundamental roles in initiating host defense against invading pathogens and discuss its pathogenic roles in multiple neuro-inflammatory diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and other neurodegenerative diseases.

scholarly journals Expression of HERV Genes as Possible Biomarker and Target in Neurodegenerative Diseases

2019 ◽  
Vol 20 (15) ◽  
pp. 3706 ◽  
Author(s):  
Antonina Dolei ◽  
Gabriele Ibba ◽  
Claudia Piu ◽  
Caterina Serra
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Disease Onset ◽  
Transgenic Animals ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Causal Connections ◽  
Multiple Sclerosis Disease ◽  
Microbial Infections ◽  
Lateral Sclerosis

Human endogenous retroviruses (HERVs) are genetic parasites, in-between genetics and environment. Few HERVs retain some coding capability. Sometimes, the host has the advantage of some HERV genes; conversely, HERVs may contribute to pathogenesis. The expression of HERVs depends on several factors, and is regulated epigenetically by stimuli such as inflammation, viral and microbial infections, etc. Increased expression of HERVs occurs in physiological and pathological conditions, in one or more body sites. Several diseases have been attributed to one or more HERVs, particularly neurological diseases. The key problem is to differentiate the expression of a HERV as cause or effect of a disease. To be used as a biomarker, a correlation between the expression of a certain HERV and the disease onset and/or behavior must be found. The greater challenge is to establish a pathogenic role. The criteria defining causal connections between HERVs and diseases include the development of animal models, and disease modulation in humans, by anti-HERV therapeutic antibody. So far, statistically significant correlations between HERVs and diseases have been achieved for HERV-W and multiple sclerosis; disease reproduction in transgenic animals was achieved for HERV-W and multiple sclerosis, and for HERV-K and amyotrophic lateral sclerosis. Clinical trials for both diseases are in progress.

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

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 610 ◽  
Author(s):  
Vincent Alcazer ◽  
Paola Bonaventura ◽  
Stephane Depil
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Interferon Response ◽  
Human Endogenous Retroviruses ◽  
Dna Production ◽  
Potential Impact ◽  
Multiple Conditions

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.

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