Induction of type I interferon by RNA viruses: cellular receptors and their substrates

Baum, Alina; García-Sastre, Adolfo

The signaling cascade of RIG-I continues to be resolved and has proven to be distinct than that of the TLR system. Similar to TLR induction, RIG-I mediated signaling cascade leads to activation of IRF3 and NF-kB (Yoneyama et al. 2004 ). However, it was shown early on that knockout MEFs of key TLR adaptors MyD88 and TRIF, do not have a defect in RIG-I mediated induction of IFN Yoneyama et al. 2004 ). The critical adaptor for RIG-I signaling was simultaneously identified by four groups as a mitochondrially located, CARD containing protein MAVS (also known as IPS-1, VISA, or Cardif). This adaptor is activated via CARD-CARD association with RIG-I and initiates a signaling cascade leading to activation of IFN-b transcription factors and subsequent production of IFN (Kawai et al. 2005; Meylan et al. 2005; Seth et al. 2005; Xu et al. 2005) .