rig-i and dsrna-induced ifnβ activationrig - i和dsrna-induced ifnβ激活.pdfVIP

RIG-I and dsRNA-Induced IFNb Activation ´ 1 1 1,2 1 Stephane Hausmann , Jean-Baptiste Marq , Caroline Tapparel , Daniel Kolakofsky *, Dominique Garcin1 1 Department Of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland, 2 Laboratory of Virology, Division of Infectious Diseases, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland Abstract Except for viruses that initiate RNA synthesis with a protein primer (e.g., picornaviruses), most RNA viruses initiate RNA synthesis with an NTP, and at least some of their viral pppRNAs remain unblocked during the infection. Consistent with this, most viruses require RIG-I to mount an innate immune response, whereas picornaviruses require mda-5. We have examined a SeV infection whose ability to induce interferon depends on the generation of capped dsRNA (without free 59 tri- phosphate ends), and found that this infection as well requires RIG-I and not mda-5. We also provide evidence that RIG-I interacts with poly-I/C in vivo, and that heteropolymeric dsRNA and poly-I/C interact directly with RIG-I in vitro, but in different ways; i.e., poly-I/C has the unique ability to stimulate the helicase ATPase of RIG-I variants which lack the C-terminal regulatory domain. Citation: Hausmann S, Marq J-B, Tapparel C, Kolakofsky D, Garcin D (2008) RIG-I and dsRNA-Induced IFNb Activation. PLoS ONE 3(12): e3965. doi:10.1371/ journal.pone.0003965 Editor: Patricia Bozza, Instituto Oswaldo Cruz and FIOCRUZ, Brazil Received August 22, 2008; Accepted November 19, 2008; Published December 30, 2008 Copyright: 2008 Hausmann et al. This is an open-access