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Cited by 1,008interferon and immune responsesChromosomal and Genetic VariationsGenomics and Chromatin Dynamics

Regulatory evolution of innate immunity through co-option of endogenous retroviruses

Open access
Chuong, Edward B., Elde, Nels C., Feschotte, Cédric·2016·Science
DOI 10.1126/science.aad5497PMC PMC4887275
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Abstract

Regulatory use of endogenous retroviruses: Mammalian genomes contain many endogenous retroviruses (ERVs), which have a range of evolutionary ages. The propagation and maintenance of these genetic elements have been attributed to their ability to contribute to gene regulation. Chuong et al. demonstrate that some ERV families are enriched in regulatory elements, so that they act as independently evolved enhancers for immune genes in both humans and mice (see the Perspective by Lynch). The analysis revealed a primate-specific element that orchestrates the transcriptional response to interferons. Selection can therefore act on selfish genetic elements to generate novel gene networks. Science , this issue p. 1083 see also p. 1029

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Crossref · 10.1126/science.aad5497

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  • Cellular products generated over the life cycle of retrotransposon activation are subject to cellular detection and clearance through the innate immune system.

    “Cellular products that are generated over the life cycle of retrotransposon activation are subject to cellular detection and clearance through the innate immune system”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Chuong et al. 2016

    The paper’s AIM2 discussion (section labeled Abstract; page unavailable) describes innate detection of cytoplasmic DNA from bacteria and viruses and an ensuing inflammatory response. It does not say that products generated during retrotransposon activation are detected or cleared by the innate immune system. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Double stranded RNAs produced by transposable element transcripts, including HERVs, can trigger a type I interferon response through the innate immune system.

    “double stranded RNAs produced by transposable element transcripts, including HERVs, can trigger a type I interferon response through the innate immune system44”

    From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [44]

    The passages labeled Abstract describe ERV-derived enhancers that regulate genes after interferon stimulation, not double-stranded RNA produced by transposable-element transcripts triggering interferon production. Searches for double-stranded RNA, ERV transcripts, and innate immune sensing found no passage in our copy addressing that mechanism. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can be potent activators of the innate immune system.

    “Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system.”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Chuong et al. 2016

    The Abstract describes endogenous retroviruses as sources of IFN-inducible enhancers that regulate immune genes, not as producers of molecules that activate innate immunity. Searches for viral-like proteins, double-stranded RNA, extrachromosomal circular DNA, and retrotransposon products did not locate a passage addressing the claimed activation mechanism. No page number is available in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cites

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Cited by

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Authors
Chuong, E. B., Elde, N. C., & Feschotte, C.
Affiliations
University of Utah (US)
Corresponding author
  • Elde, Nels C.
  • Feschotte, Cédric
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-03-04
Volume
351
Issue
6277
Pages
1083-1087
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aad5497
PMC
PMC4887275
OpenAlex
W2290849670
Cited by
1,008
References
8
Citations by year
2026: 78 · 2025: 86 · 2024: 115 · 2023: 95 · 2022: 111 · 2021: 153 · 2020: 88 · 2019: 92 · 2018: 83 · 2017: 62 · 2016: 44
FWCI
56.81
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Pew Charitable Trusts
  • NIH (GM082545, GM114514, GM112972, GM059290)
  • Howard Hughes Medical Institute
  • Jane Coffin Childs Fund
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
endogenous retroviruses, innate immunity, interferon response, transcriptional regulation, gene regulatory evolution, AIM2 inflammasome, CRISPR/Cas9 gene deletion
MeSH terms
Animals, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Immunity, Innate, Interferon-gamma, Genome, Human, Evolution, Molecular, Endogenous Retroviruses, Gene Regulatory Networks, Inflammasomes

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