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

Baum, Alina; García-Sastre, Adolfo

RIG-I can be divided into three basic domains, the N-terminal CARD, central helicase domain, and C-terminal regulatory domain (Fig. 2) . The function of these individual domains has been carefully dissected by biochemical and structural studies. The N-terminal tandem CARD domains are required for interaction with the MAVS CARD domain and downstream signaling. Even though only the terminal CARD forms the physical interaction with MAVS, both CARDs are required for signaling and constructs lacking either domain are dominant negative (Saito et al. 2007) . When expressed alone, the RIG-I CARD domain induces IFN production in a constitutive, substrate-independent manner. Interestingly, this phenomenon is only observed in the presence of wt RIG-I. When RIGI -/-cells are transfected with the CARD construct no signaling is initiated (Saito et al. 2007 ). Lack of IFN induction upon overexpression of the full length RIG-I indicates that RIG-I's native conformation is in an inactive state and requires appropriate viral stimulus to undergo a conformational change required for signaling initiation (Yoneyama et al. 2004 .