RIG-I detect genomic RNA during negative-strand RNA virus infection

Rehwinkel, J. et al. Cell 140: 397–408, 2010

Speaker: Chia-Ming Chang (張家銘)                    Time:15:10~16:00, Dec.15, 2010

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)      Place: Room 601

Abstract

Retinoic acid-inducible gene I (RIG-I) is a cytoplasmic pathogen-recognize receptor(PRR). RIG-I consists of a C-terminal domain, a central DEXD/H-box RNA helicase domain and two N-terminal caspase activation and recruitment domains (CARDs). RIG-I can detect RNA released from viruses and is activated by a ATP-dependent conformation change. RIG-I then interacts with mitochondrial adaptor proteins MAVS, which activate triggers the activation of NF-κB, interferon regulator factor -3(IRF-3) and-7. IRF-3 and IRF-7 then induce transcription of Interferons and other innate immune response genes against virus infection[1]. RLR(RIG-I-like helicase) agonists are chemically and enzymatically synthesized ribonucleotide[2]. These RNAs carry a 5’-triphophate(5’PPP) moiety that is absolutely required for their activity. Furthermore, chemically synthesized RNAoligonucleotide (25 or 70 nt long) without 5’-PPP moiety also triggers RIG-I response when annealed to it’s complementary strand. RIG-I is essential for IFN responses to negative strand virus such as Influenza virus and Sendai virus (SeV). Influenza virus is a segmented RNA virus and belongs to Orthomyxoviridae. SeV, is a Paramyxoviridae, nonsegmented genome RNA virus. Here, the authors characterized the RNA species responsible for activation RIG-I in cells infected by Influenza virus and SeV by 1. Primer extension to determine RNA species, 2. size fractionation to reveal full length genome as the consists stimulatory RNA and 3. immunoprecipitation, to reveal that stimulatory RNA associate with RIG-I and NS-1. In conclusion, the authors reveal that 5’triphosphate bearing full length viral genomics RNA constitutes the physiological source of RIG-I stimulation and IFN induction during infection with negative-strand RNA virus.

References:

1.         Yoneyama, M. and Fujita,T . RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev, 227, 54-65, 2009

2.         Schlee, M., Hartmann, E., Coch, C., Wimmenauer, V., Janke, M., Barchet, W., and Hartmamm, G.. Approaching the RNA ligand for RIG-I? Immunol Rev, 227, 66-74, 2009.