Genome and Antigenome

The genome of HDV is a small RNA of about 1,700 nucleotides in length with a circular conformation. We often refer to this RNA as single-stranded; however, based on predictions from the nucleotide sequence and certain experimental studies, we are convinced that this RNA can fold on itself via intra-molecular base pairing to form an unbranched rod-like structure. In this way, about 74% of all the nucleotides are involved in base pairing (Sect. 2.4).

The HDV genome, by definition, is the RNA species that is incorporated into new virus particles during an assembly process that depends upon envelope proteins provided by the helper hepadnavirus (see chapter by C. Sureau, this volume). However, inside a cell undergoing HDV genome replication, in addition to the genomic RNA, there are also many copies of an exactly complementary RNA, referred to as the antigenome (Chen et al. 1986). This antige-nomic RNA contains an open reading frame for a 195-amino acid species, the small delta protein (S-HDAg), which is essential for genome replication, is apparently not translated from the circular antigenomic RNA, but from a less than genome-sized, polyadenylated RNA species that is present in the cytoplasm (Sect. 2.2).

Both the genome and antigenome contain a domain that will act as a ri-bozyme. As discussed more fully in the chapter by M.D. Been (this volume), these domains are as short as 85 nucleotides in length (Ferre-D'Amare et al. 1998). They are sufficient to allow RNA cleavage in vitro, in the presence of magnesium ions. The cleavage is a site-specific trans-esterification reaction which produces a 5'-OH and a cyclic 2'-, 3'-monophosphate (Kuo et al. 1988b). This cleavage ability is needed for HDV replication (Macnaughton et al. 1993) and is considered to provide post-transcriptional cleavage of greater than unit-length HDV RNA multimers, thus releasing unit-length linear species that can be subsequently ligated to form new RNA circles (Taylor 1990). As considered in Sect. 2.4, the structures of the HDV ribozymes are different from the predicted rod-like folding.

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