RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase

HEPATITIS delta virus (HDV) is a subviral human pathogen that requires hepatitis B virus (HBV) for packaging 1,2 . Concurrent infection by HBV and HDV increases the risk of severe liver disease compared to infection with HBV alone 3 . The HDV genome is a closed circular RNA of about 1,700 bases which is replicated through an RNA intermediate, the antigenome 4 . Both RNAs can be folded into highly base-paired, rod-shaped structures, similar to the plant viroid RNAs 5 . Two forms of the sole HDV protein, hepatitis delta antigen, are derived from a single open reading frame by RNA editing; the enzymes responsible for the editing have not been characterized. Here we report that the purified enzyme dsRAD (for double-stranded-RNA-adenosine deaminase) can edit HDV antigenomic RNA in vitro . Most important, we observe that mutations in critical sequences of the antigenome have identical effects on in vitro and in vivo editing, suggesting that dsRAD, or a closely related enzyme, is responsible for editing HDV RNA in vivo .