Highlights
l Viral infection induces the formation of MAVS aggregates that potently activate IRF3
l Recombinant MAVS protein forms self-propagating fibrils
l MAVS fibrils are prion-like, converting endogenous MAVS into functional aggregates
l RIG-I and K63 polyUb chains trigger prion-like aggregates of MAVS on mitochondria
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.
Fajian Hou, Lijun Sun, Hui Zheng, Brian Skaug, Qiu-Xing Jiang, Zhijian J. Chen
Cell, 21 July 2011
Subscribe to this comment's feed
written by replica rolex sea-dweller, April 17, 2012
written by This e-mail address is being protected from spambots. You need JavaScript enabled to view it , May 14, 2012
Replica Tag Heuer Aquaracer Quartz Watches UK
written by Ringer season 1 dvd release date, May 17, 2012
A non-TV serials, Suspense story , Sarah, a twin sister to play two different personalities, also have Four Fantastic actor. Although Ringer season 1 dvd is not the youth as a selling point, but still full of dark repressed tone of the CW.
