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Jonathan P. Stoye - One of the best experts on this subject based on the ideXlab platform.
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making a virtue of necessity the pleiotropic role of human Endogenous Retroviruses in cancer
Philosophical Transactions of the Royal Society B, 2017Co-Authors: Jonathan P. Stoye, George KassiotisAbstract: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 infect...
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mammalian Endogenous Retroviruses
Microbiology spectrum, 2015Co-Authors: Dixie L. Mager, Jonathan P. StoyeAbstract:Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the Endogenous Retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles.
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resurrection of Endogenous Retroviruses in antibody deficient mice
Nature, 2012Co-Authors: George R. Young, Urszula Eksmond, Rosalba Salcedo, Lena Alexopoulou, Jonathan P. Stoye, George KassiotisAbstract:Novel pathogenic infectious Retroviruses, generated by recombination between replication-defective Endogenous Retroviruses in the absence of a functional antibody response, are identified; these recombinant Retroviruses establish infection of mouse colonies and ultimately cause cancer. Retroviruses can establish germline infections and become part of the host genome, but most of the resulting Endogenous Retroviruses, or ERVs, become inactive or transcriptionally silenced. This paper presents evidence for the emergence of novel pathogenic infectious Retroviruses generated by recombination between replication-defective ERVs in the absence of a functional antibody response. The viruses are shown to be transmissible in mouse colonies, and to give rise to a range of pathologies, including cancer. Resurrection of ERVs in the context of antibody deficiency is less pronounced in the absence of a complex microbiota. This work reveals a previously unappreciated role for immunity in the control of ERVs. The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts1, and also Endogenous Retroviruses (ERVs), comprising a substantial fraction of the mammalian genome2,3. The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks Endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic4 MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant Retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.
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Resurrection of Endogenous Retroviruses in antibody-deficient mice
Nature, 2012Co-Authors: George R. Young, Urszula Eksmond, Rosalba Salcedo, Lena Alexopoulou, Jonathan P. Stoye, George KassiotisAbstract:Novel pathogenic infectious Retroviruses, generated by recombination between replication-defective Endogenous Retroviruses in the absence of a functional antibody response, are identified; these recombinant Retroviruses establish infection of mouse colonies and ultimately cause cancer.
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Endogenous Retroviruses and the evolution of resistance to retroviral infection
Trends in Microbiology, 1997Co-Authors: Steve Best, Paul Le Tissier, Jonathan P. StoyeAbstract:The current AIDS epidemic has rekindled interest in the evolution of Retroviruses and the development of resistance to infection. Retroviruses and their vertebrate hosts have coexisted for millions of years, during which time a variety of host defence mechanisms has evolved. One repeated strategy is to use Endogenous Retroviruses to combat infection by their exogenous relatives.
George Kassiotis - One of the best experts on this subject based on the ideXlab platform.
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making a virtue of necessity the pleiotropic role of human Endogenous Retroviruses in cancer
Philosophical Transactions of the Royal Society B, 2017Co-Authors: Jonathan P. Stoye, George KassiotisAbstract: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 infect...
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Endogenous Retroviruses and the development of cancer
Journal of Immunology, 2014Co-Authors: George KassiotisAbstract:Mammalian genomes include a considerable number of Endogenous Retroviruses (ERVs), relics of ancestral infectious Retroviruses, whose proviruses have invaded the germ-line. The documented ability of infectious Retroviruses to cause cancer has greatly contributed to the discovery of ERVs. It also reinforced the concept that ERVs are causative agents of many cancers, a notion that historically has not always stood up to experimental scrutiny. The recent greater appreciation of the complexity of ERV biology and the identification of dedicated host mechanisms controlling ERV activity have revealed novel interactions between ERVs and their hosts, with the potential to cause or contribute to disease. In this review, the involvement of ERVs in cancer initiation and progression is discussed, as well as their contribution to our understanding of the process of transformation and to the invention of innovative preventive and therapeutic cancer treatments.
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resurrection of Endogenous Retroviruses in antibody deficient mice
Nature, 2012Co-Authors: George R. Young, Urszula Eksmond, Rosalba Salcedo, Lena Alexopoulou, Jonathan P. Stoye, George KassiotisAbstract:Novel pathogenic infectious Retroviruses, generated by recombination between replication-defective Endogenous Retroviruses in the absence of a functional antibody response, are identified; these recombinant Retroviruses establish infection of mouse colonies and ultimately cause cancer. Retroviruses can establish germline infections and become part of the host genome, but most of the resulting Endogenous Retroviruses, or ERVs, become inactive or transcriptionally silenced. This paper presents evidence for the emergence of novel pathogenic infectious Retroviruses generated by recombination between replication-defective ERVs in the absence of a functional antibody response. The viruses are shown to be transmissible in mouse colonies, and to give rise to a range of pathologies, including cancer. Resurrection of ERVs in the context of antibody deficiency is less pronounced in the absence of a complex microbiota. This work reveals a previously unappreciated role for immunity in the control of ERVs. The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts1, and also Endogenous Retroviruses (ERVs), comprising a substantial fraction of the mammalian genome2,3. The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks Endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic4 MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant Retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.
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Resurrection of Endogenous Retroviruses in antibody-deficient mice
Nature, 2012Co-Authors: George R. Young, Urszula Eksmond, Rosalba Salcedo, Lena Alexopoulou, Jonathan P. Stoye, George KassiotisAbstract:Novel pathogenic infectious Retroviruses, generated by recombination between replication-defective Endogenous Retroviruses in the absence of a functional antibody response, are identified; these recombinant Retroviruses establish infection of mouse colonies and ultimately cause cancer.
Avindra Nath - One of the best experts on this subject based on the ideXlab platform.
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human Endogenous Retroviruses in neurological diseases
Trends in Molecular Medicine, 2018Co-Authors: Patrick Kury, Avindra Nath, A Dolei, Julian Gold, Hans-peter Hartung, Alain Creange, Patrice N Marche, Gavin Giovannoni, Hervé PerronAbstract:The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human Endogenous Retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.
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Prehistoric enemies within: The contribution of human Endogenous Retroviruses to neurological diseases. Meeting report: “Second International Workshop on Human Endogenous Retroviruses and Disease”, Washington DC, March 13th and 14th 2017
Multiple sclerosis and related disorders, 2017Co-Authors: David Kremer, Avindra Nath, Laurent Groc, Robert Glanzman, Anthony Traboulsee, Marc S. Horwitz, Peter Göttle, Hervé Perron, Julian Gold, Hans-peter HartungAbstract:Abstract The Second International Workshop on Human Endogenous Retroviruses and Disease, Washington DC, March 13–14 2017 brought together international basic and clinical scientists investigating the involvement of human Endogenous Retroviruses (HERVs) in complex human diseases.
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first international workshop on human Endogenous Retroviruses and diseases hervs disease 2015
Mobile Dna, 2015Co-Authors: Avindra Nath, Patrick Kury, Guilherme Sciascia Do Olival, A Dolei, Hakan Karlsson, Laurent Groc, Marion Schneider, John D Kriesel, Jean Louis Touraine, François MalletAbstract:The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human Endogenous Retroviruses (HERVs) in complex human diseases.
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First international workshop on human Endogenous Retroviruses and diseases, HERVs & disease 2015.
Mobile Dna, 2015Co-Authors: Avindra Nath, Patrick Kury, Guilherme Sciascia Do Olival, A Dolei, Hakan Karlsson, Laurent Groc, Marion Schneider, John D Kriesel, Jean Louis Touraine, François MalletAbstract:The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human Endogenous Retroviruses (HERVs) in complex human diseases.
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human Endogenous Retroviruses and the nervous system
Handbook of Clinical Neurology, 2014Co-Authors: Renee Douville, Avindra NathAbstract:Abstract Within the human genome reside thousands of retrovirus-like sequences which comprise nearly 8% of the human genome. Originating from ancient Retroviruses that overcame host defense mechanisms and permanently integrated into the genomes of our early and more recent primate and hominid ancestors, these provirus remnants are referred to as human Endogenous Retroviruses (HERVs). HERV is a broad heading for numerous families of Retroviruses which were able to infect germline cells over the course of human evolution. Subsequent to integration in the genome, transmission of HERVs occurred in a Mendelian fashion, overriding the need to spread by exogenously acquired infection; however, it is clear that epigenetic and antiviral responses were essential in silencing the expression of these integrated proviruses over time. Yet, current research indicates that not all HERVs remain silent passengers, as reactivation of HERVs is associated with neurologic disorders – although they have not been shown to be causative of any human disease. This chapter focuses on the past and present activity of HERVs in humans, known triggers of HERV expression in the central nervous system, as well as putative pathologic consequences of Endogenous Retroviruses in the inception and exacerbation of neurologic disease.
H. B. Rasmussen - One of the best experts on this subject based on the ideXlab platform.
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Expression of Endogenous Retroviruses in blood mononuclear cells and brain tissue from multiple sclerosis patients.
Acta neurologica Scandinavica. Supplementum, 1997Co-Authors: H. B. Rasmussen, C Geny, L Deforges, H Perron, W Tourtelotte, A Heltberg, J ClausenAbstract:To compare the expression of Endogenous Retroviruses in MS patients and controls. Peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of matched healthy donors and five patients with other central nervous system disease. Also brain specimens from MS patients and controls were obtained. Transcripts of various Endogenous Retroviruses in these samples were detected by RNA-PCR. Several Endogenous retroviral sequences were transcribed in peripheral blood mononuclear cells and brain tissue from MS patients as well as controls. A composite transcript of an Endogenous retrovirus and a zinc finger sequence was more frequently found in healthy donors than in MS patients. Some Endogenous Retroviruses are normally transcribed in white blood cells and brain tissue. The significance of those findings, which concerned the composite transcripts of the zinc finger sequence and its associated Endogenous retrovirus is uncertain.
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Interactions between exogenous and Endogenous Retroviruses
Journal of Biomedical Science, 1997Co-Authors: H. B. RasmussenAbstract:Retroviruses are distinguished from other viruses by several features. Notably, some Retroviruses are present as normal elements in the genomes of virtually all vertebrates (Endogenous proviruses). Others are exogenous, i.e. horizontally transmitted agents, many of which cause fatal diseases. The Endogenous Retroviruses are genetically transmitted and to a large extent their significance is uncertain. However, there is evidence suggesting that they contribute to the development of diseases in several animal species. Most importantly, some Endogenous Retroviruses are capable of interacting with exogenous counterparts through a variety of different mechanisms with serious consequences to the host. Conversely, others are advantageous in that they protect against exogenous Retroviruses. In this review various types of interactions between Endogenous and exogenous Retroviruses are discussed, including receptor interference, recombination, phenotypic mixing, immunological interactions and heterologous trans -activation.
Patrick Kury - One of the best experts on this subject based on the ideXlab platform.
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human Endogenous Retroviruses in neurological diseases
Trends in Molecular Medicine, 2018Co-Authors: Patrick Kury, Avindra Nath, A Dolei, Julian Gold, Hans-peter Hartung, Alain Creange, Patrice N Marche, Gavin Giovannoni, Hervé PerronAbstract:The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human Endogenous Retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.
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first international workshop on human Endogenous Retroviruses and diseases hervs disease 2015
Mobile Dna, 2015Co-Authors: Avindra Nath, Patrick Kury, Guilherme Sciascia Do Olival, A Dolei, Hakan Karlsson, Laurent Groc, Marion Schneider, John D Kriesel, Jean Louis Touraine, François MalletAbstract:The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human Endogenous Retroviruses (HERVs) in complex human diseases.
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First international workshop on human Endogenous Retroviruses and diseases, HERVs & disease 2015.
Mobile Dna, 2015Co-Authors: Avindra Nath, Patrick Kury, Guilherme Sciascia Do Olival, A Dolei, Hakan Karlsson, Laurent Groc, Marion Schneider, John D Kriesel, Jean Louis Touraine, François MalletAbstract:The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human Endogenous Retroviruses (HERVs) in complex human diseases.