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Cited by 59interferon and immune responsesImmune Response and InflammationNF-κB Signaling Pathways

Phosphorylation of MAVS/VISA by Nemo-like kinase (NLK) for degradation regulates the antiviral innate immune response

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Li, Shang-Ze, Shu, Qi-Peng, Song, Yang, Zhang, Hui-Hui, Liu, Yi, Jin, Bing-Xue, Liuyu, Tian-Zi, Li, Chao +5 more·2019·Nature Communications
DOI 10.1038/s41467-019-11258-xPMC PMC6642205
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Abstract

MAVS is essential for antiviral immunity, but the molecular mechanisms responsible for its tight regulation remain poorly understood. Here, we show that NLK inhibits the antiviral immune response during viral infection by targeting MAVS for degradation. NLK depletion promotes virus-induced antiviral cytokine production and decreases viral replication, which is potently rescued by the reintroduction of NLK. Moreover, the depletion of NLK promotes antiviral effects and increases the survival times of mice after infection with VSV. NLK interacts with and phosphorylates MAVS at multiple sites on mitochondria or peroxisomes, thereby inducing the degradation of MAVS and subsequent inactivation of IRF3. Most importantly, a peptide derived from MAVS promotes viral-induced IFN-β production and antagonizes viral replication in vitro and in vivo. These findings provide direct insights into the molecular mechanisms by which phosphorylation of MAVS regulates its degradation and influences its activation and identify an important peptide target for propagating antiviral responses.

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Authors
Li, S.-Z., Shu, Q.-P., Song, Y., Zhang, H.-H., Liu, Y., Jin, B.-X., Liuyu, T.-Z., Li, C., Huang, X.-C., Du, R.-L., Song, W., Zhong, B., & Zhang, X.-D.
Affiliations
  • Wuhan University (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
  • Song, Wei
  • Zhong, Bo
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-07-19
Volume
10
Issue
1
Pages
3233-3233
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-11258-x
PMC
PMC6642205
OpenAlex
W2963904790
Cited by
59
References
2
Citations by year
2026: 4 · 2025: 5 · 2024: 13 · 2023: 7 · 2022: 10 · 2021: 13 · 2020: 7
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81872271)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
MAVS, Nemo-like kinase, protein phosphorylation, protein degradation, antiviral innate immunity, IRF3, interferon-beta, viral replication, vesicular stomatitis virus, mitochondrial signaling, peroxisomes, antiviral cytokines
MeSH terms
Animals, Chlorocebus aethiops, Humans, Immunity, Innate, Mice, Inbred C57BL, Phosphorylation, Protein Binding, Vero Cells, Vesicular stomatitis Indiana virus, Signal Transduction, Interferon-beta, Protein Serine-Threonine Kinases, Mice, Knockout, HCT116 Cells, Adaptor Proteins, Signal Transducing, HEK293 Cells

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