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

Baum, Alina; García-Sastre, Adolfo

An important addition to the field was the discovery that a 5 0 triphosphate (5 0 ppp) group on an RNA molecule also served as a potent activator of the interferon response and could provide an alternative/additional trigger to dsRNA (Hornung et al. 2006; Pichlmair et al. 2006) . RNA synthesis by RNA polymerases initiates with a triphosphate containing nucleotide and therefore all RNA molecules initially contain a triphosphate moiety on their 5 0 end. However, since cells generally process the synthesized RNA by either capping mRNA, removing 5 0 ppp during RNA processing, folding RNA into complex secondary structures, or packaging it into RNP complexes; exposed 5 0 ppp are likely uncommon in the cytoplasm and therefore provide an appealing viral recognition motif. The genomes of RNA viruses are known to contain uncapped, 5 0 pppcontaining RNA, although the question of whether this RNA is ever exposed to the cell during the viral lifecycle remains to be answered. Additionally, it makes sense that if viruses have evolved multiple mechanisms to hide their dsRNA, they are equally likely to protect their 5 0 ppp from antiviral sensors.