ADARs: viruses and innate immunity

Double-stranded RNA (dsRNA) functions both as a substrate of ADARs and also as a molecular trigger of innate immune responses. ADARs, adenosine deaminases that act on RNA, catalyze the deamination of adenosine (A) to produce inosine (I) in dsRNA. ADARs thereby can destablize RNA structures, because the generated I:U mismatch pairs are less stable than A:U base pairs. Additionally, I is read as G instead of A by ribosomes during translation and by viral RNA-dependent RNA polymerases during RNA replication. Members of several virus families have the capacity to produce dsRNA during viral genome transcription and replication. Sequence changes (A-G, and U-C) characteristic of A-I editing can occur during virus growth and persistence. Foreign viral dsRNA also mediates both the induction and the action of interferons. In this chapter our current understanding of the role and significance of ADARs in the context of innate immunity, and as determinants of the outcome of viral infection, will be considered.