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

Baum, Alina; García-Sastre, Adolfo

recognized by both sensors is not surprising (Strahle et al. 2007) . It is unclear whether this cell-type specific recognition of viruses is a result of differential expression of the sensors or whether cell-type specific differences in viral replication lead to different modes of recognition. Together, the above data lead to a model where MDA5 and RIG-I may possess both overlapping and distinct roles in RNA virus detection. For the vast majority of viruses and cell types, deletion of one of the sensors does not completely abrogate IFN induction (Diao et al. 2007; Kato et al. 2006) , as opposed to deletion of the common adaptor MAVS, which leads to a much more severe phenotype (Kawai et al. 2005; Meylan et al. 2005; Seth et al. 2005; Xu et al. 2005) . It is plausible that many viruses produce RNA molecules detected by both sensors and the relative abundance of these molecules dictates which receptor will play a predominant role in IFN production. An interesting question is whether most viral infections result in production of multiple distinct PAMPs (i.e. misformed RNPs and double stranded replicative intermediates) or whether the same basic PAMP is being recognized by both RIG-I and MDA5 depending on the abundance of these receptors and the substrates.