HDV Family of Self-Cleaving Ribozymes - Progress in Molecular Biology and Translational Science - page 122

hepadnaviruses. 16-18 Individuals infected with both HDV and an associated
helper virus experience an increased rate of liver cirrhosis and an increased
chance of developing liver cancer in chronic infections. 18 In these instances
of coinfection, a decrease in helper virus particles is observed upon detection
of HDV markers. 16
The HDV genome is a single-stranded circular RNA molecule of
approximately 1700 nucleotides (nt). 18 Upon infection, the RNA is tran-
scribed by a rolling-circle mechanism using host machinery to produce
its antigenomic form that is subject to one of two pathways ( Fig. 4.1 ). 19
In the first pathway, the RNA undergoes capping and polyadenylation
to yield a subgenomic sequence that serves as the mRNA for the sole
protein produced from the HDV genome, the delta antigen. 20-22 Two var-
iants of the protein are present in vivo , the small and large delta antigens. 23
These two proteins are identical in sequence except at theC-terminus, where

4

Scission

3 5

Transcription Ligation

2 1

Genomic RNA Antigenomic RNA

Processing Transcription

A
A

Ligation Transcription

6

8

Scissio n

7

Figure 4.1 The HDV life cycle. Blue lines indicate genomic (þ) and red lines indicate
antigenomic () RNA. Orange and green circles refer to genomic and antigenomic
ribozymes, respectively. During an infection cycle, the circular genomic RNA is tran-
scribed into (1) short antigenomic mRNAs coding for the delta antigen that undergo
(2) capping (black hat) and polyadenylation prior to translation, or (3) transcription into
concatemeric antigenomic RNA. The latter is (4) processed to unit-length antigenomic
transcripts by the action antigenomic HDV ribozymes, and (5) ligated using host
machinery into an antigenomic circular RNA. This circular antigenome is similarly (6)
transcribed into concatemeric genomic RNA, (7) processed into unit-length genomic
transcripts by the action of genomic HDV ribozymes, and (8) ligated using host machin-
ery to yield new genomic RNA for packaging into viral particles.