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Cited by 333interferon and immune responsesImmune Response and InflammationChromosomal and Genetic Variations

The enemy within: endogenous retroelements and autoimmune disease

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Volkman, Hannah E, Stetson, Daniel B·2014·Nature Immunology
DOI 10.1038/ni.2872PMC PMC4131434
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Abstract

Inappropriate or chronic detection of self nucleic acids by the innate immune system underlies many human autoimmune diseases. We discuss here an unexpected source of endogenous immunostimulatory nucleic acids: the reverse-transcribed cDNA of endogenous retroelements. The interplay between innate immune sensing and clearance of retroelement cDNA has important implications for the understanding of immune responses to infectious retroviruses such as human immunodeficiency virus (HIV). Furthermore, the detection of cDNA by the innate immune system reveals an evolutionary tradeoff: selection for a vigorous, sensitive response to infectious retroviruses may predispose the inappropriate detection of endogenous retroelements. We propose that this tradeoff has placed unique constraints on the sensitivity of the DNA-activated antiviral response, with implications for the interactions of DNA viruses and retroviruses with their hosts. Finally, we discuss how better understanding of the intersection of retroelement biology and innate immunity can guide the way to novel therapies for specific autoimmune diseases.

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References 97 · Cited by 333

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Authors
Volkman, H. E., & Stetson, D. B.
Affiliations
University of Washington (US)
Corresponding author
Stetson, Daniel B
ORCID
Stetson, Daniel B
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2014-04-18
Volume
15
Issue
5
Pages
415-422
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2872
PMC
PMC4131434
OpenAlex
W2078418147
Cited by
333
References
97
Citations by year
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FWCI
4.36
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (AI084914, R01AI084914)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
endogenous retroelements, autoimmune disease, innate immune recognition, retroviral infection, HIV, evolutionary trade-offs, DNA viruses, retroviruses, autoimmune disease therapy
MeSH terms
Animals, Autoimmune Diseases, Biological Evolution, Humans, Immunity, Innate, DNA, Complementary, Retroelements, Reverse Transcription, Receptors, Pattern Recognition, Host-Pathogen Interactions

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