Innate immune recognition of viral infection Kawai-2006-.pdfVIP

NATURE IMMUNOLOGY VOLUME 7 NUMBER 2 FEBRUARY 2006 131 Innate immune recognition of viral infection Taro Kawai1 Shizuo Akira1,2 Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type I interferon and inflammatory cytokines and leads to dendritic cell maturation and establishment of antiviral immunity. Cells also express cytoplasmic RNA helicases that function as alternative pattern-recognition receptors through recognition of double-stranded RNA produced during virus replication. These two classes of pattern-recognition receptor molecules are expressed in different intracellular compartments and induce type I interferon responses via distinct signaling pathways. Viral infection remains a considerable health threat. This was not always considered to be the case. The development of antibiotics and vaccina- tions brought optimism to many people that infectious diseases might be easily eradicated. The emergence of new diseases such as acquired immune deficiency syndrome, severe acute respiratory syndrome and avian influenza, along with the resurgence and expansion of existing diseases, including West Nile and Ebola hemorrhagic fevers, effectively destroyed such optimism. Moreover, although antiviral drugs that inhibit replication of viruses are now available, many viruses, includ- ing human immunodeficiency virus (HIV), mutate readily and produce resistant strains that are no longer controlled by drugs that were once effective. Furthermore, with increasing global transportation of goods and people, viral infections that would have been otherwise confined to a limited geographic region can now easily spread worldwide. The pros- pect of biological warfare by terrorists is another serious ne