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

Baum, Alina; García-Sastre, Adolfo

Proteins involved in the recognition of viral infection have only recently been identified and the initial characterization of their roles in this intricate system is just now starting to be understood. Identification of the TLR and RLR family of sensors within the last several years has provided critically important and necessary information concerning cellular recognition of RNA viruses. To date, these two receptor families are the only known systems sufficient for IFN induction in response to RNA viruses; although evidence from knockout studies point to the existence of other undiscovered receptors. Other previously described viral sensors, such as Protein Kinase R (PKR) and 2 0 -5 0 oligoadenylate synthetase (2-5 OAS) (together with RNAse L) are not sufficient for IFN production but likely play a role in mediating the IFN response. Indeed, PKR is a known dsRNA-dependent inducer of NFjB, and RNAse L has recently been shown to be responsible for generation of endogenous RNA molecules that may be stimulatory to IFN production (Kumar et al. 1994; Malathi et al. 2007 ). In addition, it has been shown that cells lacking in PKR produce lower amounts on IFN-a after infection with EMCV, supporting its modulating role in IFN production (Der and Lau 1995) . PKR's ability to be activated by 5 0 ppp RNA presents another interesting addition to PAMP/PRR interaction story (Nallagatla et al. 2007 ).