Summary and Perspectives

This chapter provides summary and perspectives of Cellular Signaling and Innate Immune Responses to RNA Virus Infections. Rapid activation of the innate immune response has a significant impact on the outcome or resolution of RNA virus infections. This occurs not only through the restrictions imposed on viral replication by the induction of interferon (IFN) α/β synthesis, but also through the controlling influence of cytokines and chemokines on the acquisition of antigen-specific adaptive immunity and inflammation at the site of infection. For this reason, pattern recognition receptors (PRRs) represent a critical first line of defense in the host response to RNA virus infections. It is increasingly clear that PRR signaling pathways share common adaptor proteins that facilitate assembly of signaling complexes that converge on two major groups of transcription factors, IFN regulatory factors (IRFs) and nuclear factor-κB (NF-κB). An emerging concept is that the NF-κB and IRF pathways are interconnected networks. Modulation by viruses of both induction and inhibition of the innate immune response has been shaped by coevolution of viruses with their hosts, to the point that it is likely that many viruses have achieved a delicate balance between induction and repression of the innate immune response that favors virus and host survival. In contrast, certain aspects of the innate response may be used by viruses for their own advantage. Recombinant viruses that lack IFN antagonism may produce highly effective and safe attenuated vaccines.