scholarly journals A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus

2021 ◽  
Author(s):  
Noémie Hamilton ◽  
Amy Clarke ◽  
Hannah Isles ◽  
Euan Carson ◽  
Jean-Pierre Levraud ◽  
...  
Keyword(s):  
Conflict Of Interest ◽  
Neurological Diseases ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Potential Conflict ◽  
Reporter Line ◽  
Disease States ◽  
Mammalian Genomes ◽  
Interest Statement

AbstractEndogenous retroviruses (ERVs) are fossils left in our genome from retrovirus infections of the past. Their sequences are part of every vertebrate genome and their random integrations are thought to have contributed to evolution. Although ERVs are mainly kept silenced by the host genome, they are found activated in multiple disease states such as auto-inflammatory disorders and neurological diseases. What makes defining their role in health and diseases challenging is the numerous copies in mammalian genomes and the lack of tools to study them. In this study, we identified 8 copies of the zebrafish endogenous retrovirus (zferv). We created and characterised the first in vivo ERV reporter line in any species. Using a combination of live imaging, flow cytometry and single cell RNA sequencing, we mapped zferv expression to early T cells and neurons. Thus, this new tool identified tissues expressing ERV in zebrafish, highlighting a potential role of ERV during brain development and strengthening the hypothesis that ERV play a role in immunity and neurological diseases. This transgenic line is therefore a suitable tool to study the function of ERV in health and diseases.FundingThis work has been supported by a European Leukodystrophy Association fellowship (ELA 2016-012F4) to NH, an MRC Programme Grant (MR/M004864/1) to SAR and . JPL is supported by Agence Nationale de la Recherche (grant ANR-16-CE20-0002-03.. Imaging was carried out in the Wolfson Light Microscopy Facility, supported by an MRC grant (G0700091) and a Wellcome Trust grant (GR077544AIA).Conflict of Interest StatementThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

scholarly journals Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2429-2435 ◽  
Author(s):  
Leonard H. Evans ◽  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Nick Weber ◽  
Kimmo Virtaneva ◽  
...  
Keyword(s):  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Gene Sequences ◽  
Endogenous Viruses ◽  
Mammalian Genomes ◽  
Leukemia Viruses ◽  
Retroviral Infections ◽  
Ecotropic Virus ◽  
Rna Transcript

ABSTRACT Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

scholarly journals MysTR: an Endogenous Retrovirus Family in Mammals That Is Undergoing Recent Amplifications to Unprecedented Copy Numbers

2005 ◽  
Vol 79 (23) ◽  
pp. 14698-14707 ◽  
Author(s):  
Michael A. Cantrell ◽  
Martina M. Ederer ◽  
Issac K. Erickson ◽  
Vicki J. Swier ◽  
Robert J. Baker ◽  
...  
Keyword(s):  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
South American ◽  
Coding Regions ◽  
Copy Numbers ◽  
Species Analysis ◽  
Outgroup Species ◽  
Mammalian Genomes ◽  
Oryzomys Palustris

ABSTRACT A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in Oryzomys palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed gag, pro, and pol coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in O. palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P.maniculatus leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.

scholarly journals Characterization of Endogenous Retroviruses in Sheep

2003 ◽  
Vol 77 (20) ◽  
pp. 11268-11273 ◽  
Author(s):  
Nikolai Klymiuk ◽  
Mathias Müller ◽  
Gottfried Brem ◽  
Bernhard Aigner
Keyword(s):  
Endogenous Retrovirus ◽  
Ovis Aries ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
In Vivo Experiments ◽  
Pregnant Sheep ◽  
Reading Frames

ABSTRACT Endogenous retrovirus (ERV) sequences have been found in all mammals. In vitro and in vivo experiments revealed ERV activation and cross-species infection in several species. Sheep (Ovis aries) are used for various biotechnological purposes; however, they have not yet been comprehensively screened for ERV sequences. Therefore, the aim of the study was to classify the ERV sequences in the ovine genome (OERV) by analyzing the retroviral pro-pol sequences. Three OERV β families and nine OERV γ families were revealed. Novel open reading frames (ORF) in the amplified proviral fragment were found in one OERV β family and two OERV γ families. Hybrid OERV produced by putative recombination events were not detected. Quantitative analysis of the OERV sequences in the ovine genome revealed no relevant variations in the endogenous retroviral loads of different breeds. Expression analysis of different tissues from fetal and pregnant sheep detected mRNA from both gammaretrovirus families, showing ORF fragments. Thus, the release of retroviruses from sheep cells cannot be excluded.

scholarly journals Human APOBEC3G Prevents Emergence of Infectious Endogenous Retrovirus in Mice

2019 ◽  
Vol 93 (20) ◽  
Author(s):  
Rebecca S. Treger ◽  
Maria Tokuyama ◽  
Huiping Dong ◽  
Karen Salas-Briceno ◽  
Susan R. Ross ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Toll Like Receptor ◽  
Restriction Factors ◽  
Cytidine Deaminases ◽  
Endogenous Loci ◽  
Human Apobec3g

ABSTRACT Endogenous retroviruses (ERV) are found throughout vertebrate genomes, and failure to silence their activation can have deleterious consequences on the host. Mutation and subsequent disruption of ERV loci is therefore an indispensable component of the cell-intrinsic defenses that maintain the integrity of the host genome. Abundant in vitro and in silico evidence have revealed that APOBEC3 cytidine-deaminases, including human APOBEC3G (hA3G), can potently restrict retrotransposition; yet, in vivo data demonstrating such activity is lacking, since no replication-competent human ERV have been identified. In mice deficient for Toll-like receptor 7 (TLR7), transcribed ERV loci can recombine and generate infectious ERV. In this study, we show that ectopic expression of hA3G can prevent the emergence of replication-competent, infectious ERV in Tlr7−/− mice. Mice encode one copy of Apobec3 in their genome. ERV reactivation in Tlr7−/− mice was comparable in the presence or absence of Apobec3. In contrast, expression of a human APOBEC3G transgene abrogated emergence of infectious ERV in the Tlr7−/− background. No ERV RNA was detected in the plasma of hA3G+ Apobec3−/− Tlr7−/− mice, and infectious ERV virions could not be amplified through coculture with permissive cells. These data reveal that hA3G can potently restrict active ERV in vivo and suggest that expansion of the APOBEC3 locus in primates may have helped to provide for the continued restraint of ERV in the human genome. IMPORTANCE Although APOBEC3 proteins are known to be important antiviral restriction factors in both mice and humans, their roles in the restriction of endogenous retroviruses (ERV) have been limited to in vitro studies. Here, we report that human APOBEC3G expressed as a transgene in mice prevents the emergence of infectious ERV from endogenous loci. This study reveals that APOBEC3G can powerfully restrict active retrotransposons in vivo and demonstrates how transgenic mice can be used to investigate host mechanisms that inhibit retrotransposons and reinforce genomic integrity.

Potential Conflict-of-Interest Statement

1986 ◽  
Vol 66 (7) ◽  
pp. 1071-1071
Author(s):  
Marilyn J. Lister
Keyword(s):  
Conflict Of Interest ◽  
Potential Conflict ◽  
Interest Statement

scholarly journals On transposons and totipotency

2020 ◽  
Vol 375 (1795) ◽  
pp. 20190339 ◽  
Author(s):  
Maria-Elena Torres-Padilla
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Host Genome ◽  
The Past ◽  
Stage Of Development ◽  
Mammalian Genomes

Our perception of the role of the previously considered ‘selfish’ or ‘junk’ DNA has been dramatically altered in the past 20 years or so. A large proportion of this non-coding part of mammalian genomes is repetitive in nature, classified as either satellites or transposons. While repetitive elements can be termed selfish in terms of their amplification, such events have surely been co-opted by the host, suggesting by itself a likely altruistic function for the organism at the subject of such natural selection. Indeed numerous examples of transposons regulating the functional output of the host genome have been documented. Transposons provide a powerful framework for large-scale relatively rapid concerted regulatory activities with the ability to drive evolution. Mammalian totipotency has emerged as one key stage of development in which transposon-mediated regulation of gene expression has taken centre stage in the past few years. During this period, large-scale (epigenetic) reprogramming must be accomplished in order to activate the host genome. In mice and men, one particular element murine endogenous retrovirus with leucine tRNA primer (MERVL) (and its counterpart human ERVL (HERVL)) appears to have acquired roles as a key driving force in this process. Here, I will discuss and interpret the current knowledge and its implications regarding the role of transposons, particularly of long interspersed nuclear elements (LINE-1s) and endogenous retroviruses (ERVs), in the regulation of totipotency. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

scholarly journals Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1699
Author(s):  
Anna Andrea Lauer ◽  
Lea Victoria Griebsch ◽  
Sabrina Melanie Pilz ◽  
Daniel Janitschke ◽  
Elena Leoni Theiss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Neurological Diseases ◽  
Neuroblastoma Cells ◽  
Lipid Homeostasis ◽  
Disease States ◽  
Ethanolamine Plasmalogen ◽  
Inflammatory Processes

Vitamin D3 hypovitaminosis is associated with several neurological diseases such as Alzheimer’s disease, Parkinson’s disease or multiple sclerosis but also with other diseases such as cancer, diabetes or diseases linked to inflammatory processes. Importantly, in all of these diseases lipids have at least a disease modifying effect. Besides its well-known property to modulate gene-expression via the VDR-receptor, less is known if vitamin D hypovitaminosis influences lipid homeostasis and if these potential changes contribute to the pathology of the diseases themselves. Therefore, we analyzed mouse brain with a mild vitamin D hypovitaminosis via a targeted shotgun lipidomic approach, including phosphatidylcholine, plasmalogens, lyso-phosphatidylcholine, (acyl-/acetyl-) carnitines and triglycerides. Alterations were compared with neuroblastoma cells cultivated in the presence and with decreased levels of vitamin D. Both in cell culture and in vivo, decreased vitamin D level resulted in changed lipid levels. While triglycerides were decreased, carnitines were increased under vitamin D hypovitaminosis suggesting an impact of vitamin D on energy metabolism. Additionally, lyso-phosphatidylcholines in particular saturated phosphatidylcholine (e.g., PC aa 48:0) and plasmalogen species (e.g., PC ae 42:0) tended to be increased. Our results suggest that vitamin D hypovitaminosis not only may affect gene expression but also may directly influence cellular lipid homeostasis and affect lipid turnover in disease states that are known for vitamin D hypovitaminosis.

scholarly journals Activation of endogenous retroviruses during brain development causes neuroinflammation

2020 ◽  
Author(s):  
Marie E Jönsson ◽  
Raquel Garza ◽  
Yogita Sharma ◽  
Rebecca Petri ◽  
Erik Södersten ◽  
...  
Keyword(s):  
Brain Development ◽  
Transcriptional Activation ◽  
Neural Progenitor Cells ◽  
Large Fraction ◽  
Endogenous Retroviruses ◽  
Adult Brain ◽  
Potential Trigger ◽  
Mammalian Genomes ◽  
The Brain

AbstractEndogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo deletion of Trim28 in cortical NPCs during mouse brain development resulted in viable offspring expressing high levels of ERV expression in excitatory neurons in the adult brain. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.

scholarly journals Study of Full-Length Porcine Endogenous Retrovirus Genomes with Envelope Gene Polymorphism in a Specific-Pathogen-Free Large White Swine Herd

2000 ◽  
Vol 74 (18) ◽  
pp. 8575-8581 ◽  
Author(s):  
Steffi Bösch ◽  
Claire Arnauld ◽  
André Jestin
Keyword(s):  
Endogenous Retrovirus ◽  
Amino Acid Sequences ◽  
Full Length ◽  
Endogenous Retroviruses ◽  
Envelope Gene ◽  
Specific Pathogen Free ◽  
Large White ◽  
Porcine Endogenous Retrovirus ◽  
Specific Pathogen

ABSTRACT Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate for pig to human xenotransplantation. Still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier, J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681–682, 1997). Here we addressed the question of PERV distribution in a French Large White SPF pig herd in vivo. First, PCR screening for previously described PERV envelope genes envA, envB, and envC(D. E. Akiyoshi, M. Denaro, H. Zhu, J. L. Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503–4507, 1998; Le Tissier et al., op. cit.). demonstrated ubiquity of envAand envB sequences, whereas envC genes were absent in some animals. On this basis, selective out-breeding of pigs of remote origin might be a means to reduce proviral load in organ donors. Second, we investigated PERV genome carriage inenvC negative swine. Eleven distinct full-length PERV transcripts were isolated. The sequence of the complete envelope open reading frame was determined. The deduced amino acid sequences revealed the existence of four clones with functional and five clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence of easily detectable levels of PERV variants in different pig tissues in vivo heightens the need to assess PERV transmission in xenotransplantation animal models.

scholarly journals Human endogenous retrovirus HERV-K113 is capable of producing intact viral particles

2008 ◽  
Vol 89 (2) ◽  
pp. 567-572 ◽  
Author(s):  
Klaus Boller ◽  
Kurt Schönfeld ◽  
Stefanie Lischer ◽  
Nicole Fischer ◽  
Andreas Hoffmann ◽  
...  
Keyword(s):  
Germ Cell ◽  
Particle Production ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Germ Cell Tumours ◽  
Typical Structure ◽  
Viral Particles ◽  
Baculovirus Expression Vector

Of all human endogenous retroviruses known today, HERV-K is the only one that has been shown to produce viral particles. While the first of the approximately 30 HERV-K sequences integrated into the human genome more than 40 million years ago, evidence is accumulating that HERV-K was active more recently, provirus HERV-K113 being the youngest sequence found. However, it is unclear which HERV-K sequences code for the viral particles that are produced by human germ-cell tumours or melanomas. Here, we show that the provirus HERV-K113, cloned into a baculovirus expression vector, is capable of producing intact particles of retroviral morphology, exhibiting the typical structure of those particles that were characterized in cell lines derived from human germ-cell tumours. Thus, the HERV-K113 sequence is a candidate for particle production in vivo and for an active human endogenous retrovirus of today.

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