Related Experiment Video
Updated: Jul 19, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
WDR77 inhibits prion-like aggregation of MAVS to limit antiviral innate immune response
Jiaxin Li1, Rui Zhang1, Changwan Wang1,2
1State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, 200031, China.
Abstract:
RIG-I-MAVS signaling pathway plays a crucial role in defending against pathogen infection and maintaining immune balance. Upon detecting viral RNA, RIG-I triggers the formation of prion-like aggregates of the adaptor protein MAVS, which then activates the innate antiviral immune response. However, the mechanisms that regulate the aggregation of MAVS are not yet fully understood. Here, we identified WDR77 as a MAVS-associated protein, which negatively regulates MAVS aggregation. WDR77 binds to MAVS proline-rich region through its WD2-WD3-WD4 domain and inhibits the formation of prion-like filament of recombinant MAVS in vitro. In response to virus infection, WDR77 is recruited to MAVS to prevent the formation of its prion-like aggregates and thus downregulate RIG-I-MAVS signaling in cells. WDR77 deficiency significantly potentiates the induction of antiviral genes upon negative-strand RNA virus infections, and myeloid-specific Wdr77-deficient mice are more resistant to RNA virus infection. Our findings reveal that WDR77 acts as a negative regulator of the RIG-I-MAVS signaling pathway by inhibiting the prion-like aggregation of MAVS to prevent harmful inflammation.
Insights
WDR77 inhibits MAVS aggregation, a key step in antiviral immunity. This discovery reveals WDR77 as a negative regulator of the RIG-I-MAVS pathway, preventing excessive inflammation during viral infections.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- The RIG-I-MAVS signaling pathway is essential for innate antiviral immunity.
- MAVS protein aggregation into prion-like filaments is critical for RIG-I pathway activation.
- Mechanisms regulating MAVS aggregation remain incompletely understood.
Purpose of the Study:
- To identify novel regulators of MAVS aggregation.
- To elucidate the role of WDR77 in the RIG-I-MAVS signaling pathway.
- To investigate the therapeutic potential of targeting WDR77 in viral infections.
Main Methods:
- Co-immunoprecipitation assays to identify MAVS-interacting proteins.
- In vitro assays using recombinant MAVS to study aggregation.
- Viral infection models in cell culture and mice.
- Analysis of antiviral gene induction in WDR77-deficient cells and mice.
Main Results:
- WDR77 was identified as a MAVS-binding protein.
- WDR77 inhibits MAVS prion-like filament formation in vitro.
- WDR77 negatively regulates RIG-I-MAVS signaling by preventing MAVS aggregation.
- WDR77 deficiency enhances antiviral gene expression and increases resistance to RNA virus infection in mice.
Conclusions:
- WDR77 acts as a negative regulator of the RIG-I-MAVS pathway.
- WDR77 prevents harmful inflammation by inhibiting MAVS aggregation.
- Targeting WDR77 may offer a strategy for enhancing antiviral immunity.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:23The Antiviral System of Bacteria and Archaea: CRISPR
02:15Experimental RNAi