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Cited by 12interferon and immune responsesImmune Response and InflammationVirology and Viral Diseases

Modulation of Innate Immune Signalling by Lipid-Mediated MAVS Transmembrane Domain Oligomerization

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Nobre, Luis, Wise, Daniel, Ron, David, Volmer, Romain·2015·PLOS ONE
DOI 10.1371/journal.pone.0136883PMC PMC4552940
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Abstract

RIG-I-like receptors detect viral RNA in infected cells and promote oligomerization of the outer mitochondrial membrane protein MAVS to induce innate immunity to viral infection through type I interferon production. Mitochondrial reactive oxygen species (mROS) have been shown to enhance anti-viral MAVS signalling, but the mechanisms have remained obscure. Using a biochemical oligomerization-reporter fused to the transmembrane domain of MAVS, we found that mROS inducers promoted lipid-dependent MAVS transmembrane domain oligomerization in the plane of the outer mitochondrial membrane. These events were mirrored by Sendai virus infection, which similarly induced lipid peroxidation and promoted lipid-dependent MAVS transmembrane domain oligomerization. Our observations point to a role for mROS-induced changes in lipid bilayer properties in modulating antiviral innate signalling by favouring the oligomerization of MAVS transmembrane domain in the outer-mitochondrial membrane.

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  • MAVS is associated with neuroinflammation and synaptic loss in AD through interferon I-driven inflammation.

    “The eRNA ENSR00000133987 putatively targets the Mitochondrial Antiviral Signaling Protein (MAVS) gene, which is associated with neuroinflammation and synaptic loss in AD through interferon I–driven inflammation (Fig. 3E) (52, 53).”

    From Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains (2025) · cites this paper as [53]

    The Introduction (page unavailable) describes MAVS-mediated type I interferon signalling in an antiviral response, and the Results (page unavailable) report increased interferon-β transcription under the tested conditions. The paper does not establish that MAVS causes neuroinflammation or synaptic loss in Alzheimer’s disease through that pathway. (LLM, conf=0.88)

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References 49 · Cited by 12

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Authors
Nobre, L., Wise, D., Ron, D., & Volmer, R.
Affiliations
  • University of Cambridge (GB)
  • École Nationale Vétérinaire de Toulouse (FR)
Corresponding author
Volmer, Romain
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-08-28
Volume
10
Issue
8
Pages
e0136883
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0136883
PMC
PMC4552940
OpenAlex
W1937713800
Cited by
12
References
49
Citations by year
2025: 2 · 2024: 1 · 2023: 2 · 2021: 3 · 2019: 2 · 2018: 2
FWCI
0.33
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (093764, 100140, 084812/Z/08/Z, 100140/Z/12/Z, 093764/Z/10/Z, 084812)
  • European Commission (277713)
  • Medical Research Council
  • Cambridge Institute for Medical Research, University of Cambridge (100140)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
MAVS, mitochondrial reactive oxygen species, lipid peroxidation, RIG-I-like receptors, innate immune signaling, type I interferon, Sendai virus, mitochondrial outer membrane, lipid bilayer properties, antiviral innate immunity
MeSH terms
Humans, Immunity, Innate, Mitochondria, Respirovirus Infections, Recombinant Fusion Proteins, Lipid Peroxidation, Reactive Oxygen Species, Sendai virus, Adaptor Proteins, Signal Transducing, Protein Interaction Domains and Motifs, HEK293 Cells

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