C. Background on HDV Secondary Structure:The RNA genome has a very particular secondary structure, and the significance of particular structures at various sites is still being determined. A key step in the replication of HDV involves editing of a region called the amber/W site by host enzyme ADAR1 (adenosine deaminase) that causes the mutation of a UAG stop codon on HDAg-S to a UGG tryptophan codon, allowing for the production of HDAg-L that inhibits replication but allows for the formation of new virions.

Jayan GC, and JL Casey. 2005. Effects of conserved RNA secondary structures on hepatitis delta virus genotype I RNA editing, replication, and virus production. J Virology. 79(17): 11187-93.

Jayan and Casey examined a specific portion of the genome: the region 3' of the amber/W editing site. This region normally has a very particular secondary structure consisting of a highly conserved region that is primarily base paired, but also includes asymmetric internal loops and single-base bulges. Jayan and Casey investigated the effects of increased and decreased base pairing in this region on activities of the virus. They found that increased base pairing in this region increased editing, and this the number of HDAg-L antigens, promoting replication inhibition, and eventually reduced virus production. Thus the natural nature of the secondary structure of the RNA in this region is designed to maximize replication and secretion rather than editing and HDAg-L production. Presumably, this is the "goal" of the virus in general.