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Updated: Feb 28, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling
Nan Qi1, Yuheng Shi1, Rui Zhang1
1State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Abstract:
In response to virus infection, RIG-I-like receptors (RLRs) sense virus RNA and induce MAVS to form prion-like aggregates to further propagate antiviral signalling. Although monomeric MAVS recombinant protein can assemble into prion-like filaments spontaneously in vitro, endogenous MAVS in cells is prevented from aggregation until viral infection. The mechanism preventing cellular MAVS from spontaneous aggregation is unclear. Here we show that multiple N-terminal truncated isoforms of MAVS are essential in preventing full-length MAVS from spontaneous aggregation through transmembrane domain-mediated homotypic interaction. Without these shorter isoforms, full-length MAVS is prone to spontaneous aggregation and Nix-mediated mitophagic degradation. In the absence of N-terminally truncated forms, blocking Nix-mediated mitophagy stabilizes full-length MAVS, which aggregates spontaneously and induces the subsequent expression of type I interferon and other proinflammatory cytokines. Our data thus uncover an important mechanism preventing spontaneous aggregation of endogenous MAVS to avoid accidental activation of antiviral innate immune signalling.
Insights
Shorter MAVS protein forms prevent spontaneous aggregation of full-length MAVS, avoiding accidental activation of antiviral immune responses. This discovery clarifies a key mechanism in innate immunity regulation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- RIG-I-like receptors (RLRs) initiate antiviral signaling upon sensing viral RNA.
- MAVS aggregates into prion-like structures to propagate antiviral signals.
- The mechanism preventing spontaneous MAVS aggregation in cells is unknown.
Purpose of the Study:
- To elucidate the mechanism preventing spontaneous aggregation of endogenous MAVS.
- To understand how cellular MAVS aggregation is regulated before viral infection.
Main Methods:
- Investigated the role of N-terminal truncated MAVS isoforms.
- Analyzed MAVS aggregation using transmembrane domain-mediated homotypic interactions.
- Studied Nix-mediated mitophagic degradation pathways.
Main Results:
- N-terminally truncated MAVS isoforms prevent full-length MAVS aggregation via transmembrane domain interactions.
- Absence of shorter isoforms leads to spontaneous MAVS aggregation and Nix-mediated degradation.
- Inhibiting Nix-mediated mitophagy in the absence of truncated forms causes MAVS aggregation and cytokine induction.
Conclusions:
- N-terminally truncated MAVS isoforms are crucial for preventing spontaneous MAVS aggregation.
- This regulation prevents accidental activation of innate antiviral immune signaling.
- The findings reveal a novel mechanism controlling MAVS-mediated immunity.
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