MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response

Fajian Hou, Lijun Sun, Hui Zheng, Brian Skaug, Qiu Xing Jiang, Zhijian J. Chen

Research output: Contribution to journalArticle

548 Citations (Scopus)

Abstract

In response to viral infection, RIG-I-like RNA helicases bind to viral RNA and activate the mitochondrial protein MAVS, which in turn activates the transcription factors IRF3 and NF-κB to induce type I interferons. We have previously shown that RIG-I binds to unanchored lysine-63 (K63) polyubiquitin chains and that this binding is important for MAVS activation; however, the mechanism underlying MAVS activation is not understood. Here, we show that viral infection induces the formation of very large MAVS aggregates, which potently activate IRF3 in the cytosol. We find that a fraction of recombinant MAVS protein forms fibrils that are capable of activating IRF3. Remarkably, the MAVS fibrils behave like prions and effectively convert endogenous MAVS into functional aggregates. We also show that, in the presence of K63 ubiquitin chains, RIG-I catalyzes the conversion of MAVS on the mitochondrial membrane to prion-like aggregates. These results suggest that a prion-like conformational switch of MAVS activates and propagates the antiviral signaling cascade.

Original languageEnglish (US)
Pages (from-to)448-461
Number of pages14
JournalCell
Volume146
Issue number3
DOIs
StatePublished - Aug 5 2011

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Prions
Innate Immunity
Antiviral Agents
Virus Diseases
Chemical activation
Polyubiquitin
RNA Helicases
Recombinant proteins
Interferon Type I
Mitochondrial Proteins
Viral RNA
Mitochondrial Membranes
Ubiquitin
Recombinant Proteins
Cytosol
Lysine
Transcription Factors
Switches
Membranes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. / Hou, Fajian; Sun, Lijun; Zheng, Hui; Skaug, Brian; Jiang, Qiu Xing; Chen, Zhijian J.

In: Cell, Vol. 146, No. 3, 05.08.2011, p. 448-461.

Research output: Contribution to journalArticle

Hou, Fajian ; Sun, Lijun ; Zheng, Hui ; Skaug, Brian ; Jiang, Qiu Xing ; Chen, Zhijian J. / MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. In: Cell. 2011 ; Vol. 146, No. 3. pp. 448-461.
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