Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection
Open accessAbstract
While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-β and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/-mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-β transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.
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During viral VSV infection, ADAP interacts with RIG-I to modulate type I interferon responses in macrophages.
“During viral VSV infection, ADAP interacts with RIG-I to modulate type I interferon responses in macrophages [20].”
From Inhibition of SPI1 by ADAP Regulates S100A8/A9 Signaling in Macrophages to Control the Development of Colitis (2026) · cites this paper as [20]
The Discussion reports that ADAP deficiency reduces type I interferon production in macrophages after VSV infection and that ADAP interacts with RIG-I during RNA-virus infection. The Results section on ADAP–RIG-I interaction tests that interaction during SeV infection, not specifically during VSV infection, so the VSV-specific interaction is not established by our copy. (LLM, conf=0.84)
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“During viral VSV infection, ADAP interacts with RIG-I to modulate type I interferon responses in macrophages [20].”
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- Authors
- Wang, Y., Feng, H., Li, X., Ruan, Y., Guo, Y., Cui, X., Zhang, P., Li, Y., Wang, X., Wang, X., Wei, L., Yi, Y., Zhang, L., Yang, X., & Liu, H.
- Affiliations
- Soochow University (CN)
- Zhejiang A & F University (CN)
- Xi’an Jiaotong-Liverpool University (CN)
- Second Affiliated Hospital of Soochow University (CN)
- Corresponding author
- Liu, Hebin
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2024-05-22
- Volume
- 20
- Issue
- 5
- Pages
- e1012230
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC11111093
- OpenAlex
- W4398199170
- Cited by
- 7
- References
- 55
- Citations by year
- 2026: 3 · 2025: 4
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Natural Science Foundation of Jiangsu Higher Education Institution-Key Program (21KJA310002)
- Suzhou Key Program Special Funds in XJTLU (KSF-A-21, KSF-E-30)
- Soochow University Research Development Funds (Q424900220)
- National Natural Science Foundation of China (31470840)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- 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 › Molecular Biology › RNA regulation and disease
- Keywords
- ADAP, RIG-I, ISGylation, ISG15, type I interferon response, macrophages, RNA virus infection, IRF3 phosphorylation, TBK1, MDA5, antiviral innate immunity, viral RNA sensing
- MeSH terms
- DEAD Box Protein 58, Animals, Humans, Interferon Type I, Macrophages, Mice, Inbred C57BL, Receptors, Immunologic, RNA Virus Infections, RNA Viruses, Ubiquitins, Cytokines, Interferon-beta, Mice, Knockout, Adaptor Proteins, Signal Transducing, Interferon Regulatory Factor-3, Mice
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