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

Baum, Alina; García-Sastre, Adolfo

The requirement for viral replication has been supported by numerous studies, even though it does appear that under certain conditions completely inactive virus is capable of inducing IFN (Hidmark et al. 2005) . It remains to be determined whether this induction by inactivated virus is due to incomplete inactivation, exposure of viral RNA resulting from physical damage to the virions, or if other viral components are capable of being recognized by the cell. In addition to viral RNA, viral proteins and ribonucleoprotein (RNP) complexes have been implicated in IFN induction. When introduced into cells, purified RNP complexes do induce an IFN response (tenOever et al. 2002 (tenOever et al. , 2004 . However, since it is extremely difficult to demonstrate that intact RNPs are introduced into cells, differentiation between RNP recognition and naked RNA recognition remains elusive. A few examples of viral protein recognition do exist. Hepatitis C Virus (HCV) NS5A protein has been shown to activate nuclear factor-jB (NF-jB) when expressed in cells (Waris et al. 2002) . In addition, the F protein of respiratory syncytial virus (RSV) is well characterized to be capable of inducing proinflammatory cytokines through TLR4 (Kurt-Jones et al. 2000) . However, it is unlikely that viral proteins alone are sufficient for induction of an antiviral response based on their wide diversity and biochemical similarity to cellular proteins. A more plausible scenario is that during a viral infection, multiple signals are recognized by different sensors, which in synergy, alert the cell to the presence of a viral pathogen.