The HDV Virion

The HDV particle is composed of a single-stranded circular 1.7 kb RNA genome, small and large delta antigen (S- and L-HDAg), which together are surrounded by a lipid envelope containing the HBV surface antigen proteins (HBsAgs). The fully assembled particle diameter is about 36 nm. Sequencing of isolates from around the world has led to a classification into three genotypes-I, II, and III-based on sequence variation (Casey 1996), and recent data suggests the existence of up to four additional genotypes (Radjef et al. 2004) (see the chapter by P. Deny, this volume). The two major isoforms of delta antigen, termed small and large, are identical in sequence except that L-HDAghas an extra 19 amino acids atits carboxyl (C-) terminus. As detailed by W.-H. Huang et al. (this volume), this addition is the result of a specific RNA editing event which occurs during replication of the HDV genome and converts the S-HDAg stop codon into a tryptophan codon which then allows translation to proceed to the next downstream stop codon. The presence of these extra C-terminal amino acids dramatically changes the function of delta antigen. For example, while S-HDAg promotes HDV genome replication, the L-HDAg can act as a potent transdominant inhibitor (Chao et al. 1990; Glenn and White 1991; Sato et al. 2004). The two isoforms also have differences in their ability to transactivate heterologous genes (Wei and Ganem 1998). As discussed in the next section, perhaps the most striking functional difference between these isoforms has emerged from studies of HDV assembly.

0 0

Post a comment