Co-option of endogenous viral sequences for host cell function

Frank, John A; Feschotte, Cédric

doi:10.1016/j.coviro.2017.07.021

Cited by 141 publications

(149 citation statements)

References 100 publications

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“…Indeed, pathogenicity determinants typically are carried by integrated or extrachromosomal MGE. Thus, the perception of iMGE as 'junk DNA' or 'genomic parasites' is changing to the concept of iMGE being major agents of molecular innovation and environmental adaptation of cellular organisms (Omelchenko et al, 2005;Frost and Koraimann, 2010;Frank and Feschotte, 2017;Jangam et al, 2017;Koonin and Krupovic, 2018). Typically, MGE integration leaves a molecular scar in the cellular genome which manifests as direct repeats (DR) flanking the iMGE (Grindley et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Integrated mobile genetic elements in Thaumarchaeota

Krupovìč

Makarova

Wolf

et al. 2019

Environmental Microbiology

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Summary To explore the diversity of mobile genetic elements (MGE) associated with archaea of the phylum Thaumarchaeota, we exploited the property of most MGE to integrate into the genomes of their hosts. Integrated MGE (iMGE) were identified in 20 thaumarchaeal genomes amounting to 2 Mbp of mobile thaumarchaeal DNA. These iMGE group into five major classes: (i) proviruses, (ii) casposons, (iii) insertion sequence‐like transposons, (iv) integrative‐conjugative elements and (v) cryptic integrated elements. The majority of the iMGE belong to the latter category and might represent novel families of viruses or plasmids. The identified proviruses are related to tailed viruses of the order Caudovirales and to tailless icosahedral viruses with the double jelly‐roll capsid proteins. The thaumarchaeal iMGE are all connected within a gene sharing network, highlighting pervasive gene exchange between MGE occupying the same ecological niche. The thaumarchaeal mobilome carries multiple auxiliary metabolic genes, including multicopper oxidases and ammonia monooxygenase subunit C (AmoC), and stress response genes, such as those for universal stress response proteins (UspA). Thus, iMGE might make important contributions to the fitness and adaptation of their hosts. We identified several iMGE carrying type I‐B CRISPR‐Cas systems and spacers matching other thaumarchaeal iMGE, suggesting antagonistic interactions between coexisting MGE and symbiotic relationships with the ir archaeal hosts.

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Section: Introductionmentioning

confidence: 99%

Integrated mobile genetic elements in Thaumarchaeota

Krupovìč

Makarova

Wolf

et al. 2019

Environmental Microbiology

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“…However, in tumors (and presumably under the influence of elevated interferon-gamma levels) retroviral genes such as the gp70 protein of murine leukemia virus are actively transcribed and give rise to peptides, that can be presented onto MHC class I proteins. Some retroviral antigens are also endowed with transposon activity (27,28).…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response against the AH1 tumor rejection antigen

Probst

Stringhini

Neri

2019

Preprint

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The possibility to cure immunocompetent mice bearing murine CT26 colorectal tumors using cytokinebased therapeutics allows to study the tumor rejection process at a molecular level. Following treatment with L19-mIL12 or F8-mTNF, two antibody fusion proteins which preferentially concentrate a murine cytokine payload at the tumor site, CT26 tumors could be cured in a process that crucially relies on CD8+ T cells. In both settings, the AH1 peptide (derived from the gp70 envelop protein of murine leukemia virus) acted as the main tumor rejection antigen and ~50% of CD8+ T cells in the tumor mass are AH1-specific after therapy. In order to characterize the clonality of the T cell response after successful antibody-cytokine immunotherapy, we isolated CD8+ T cells from tumors and submitted them to T cell receptor (TCR) sequencing. As expected, different TCR sequences were found in different mice, as these molecules originate from a stochastic rearrangement process. CD8+ T cells featuring the ten most abundant TCR sequences represented more than 60% of total CD8+ T cell clones in the tumor mass, but less than 10% in the spleen. Looking at sorted CD8+ T cells from individual animals, AH1-specific TCRs were consistently found among the most abundant sequences.Collectively, these data suggest that the antitumor response driven by two different antibody-cytokine fusions proceeds through an oligoclonal expansion and activation of tumor-infiltrating CD8+ T cells.

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“…Increasing evidence suggests that regulatory functions of TEs are not limited to provision of cis ‐elements at the DNA level, but that TE RNA and/or protein products may adopt functional roles in cells. In several organisms, ERV‐derived products have been shown to interfere with or inhibit viral infections, in part by competing with exogenous viral proteins to inhibit replication . Interestingly, these same interactions may also drive the evolution or diversification of ERV proteins .…”

Section: Emerging Evidence For Essential Roles For Expressed Tes Durimentioning

confidence: 99%

“…In several organisms, ERV‐derived products have been shown to interfere with or inhibit viral infections, in part by competing with exogenous viral proteins to inhibit replication . Interestingly, these same interactions may also drive the evolution or diversification of ERV proteins . RNA derived from intronic Alu elements has been suggested to be important for nucleolar structure and Pol I transcription, with splice‐sites contained within Alu RNA also contributing to alternative splicing events .…”

Section: Emerging Evidence For Essential Roles For Expressed Tes Durimentioning

confidence: 99%

What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

2020

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Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis‐elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.

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Co-option of endogenous viral sequences for host cell function

Cited by 141 publications

References 100 publications

Integrated mobile genetic elements in Thaumarchaeota

Integrated mobile genetic elements in Thaumarchaeota

Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response against the AH1 tumor rejection antigen

What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation

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