Insight into the Contribution and Disruption of Host Processes during HDV Replication

Abstract

Hepatitis delta virus (HDV) is unique among animal viruses. HDV is a satellite virus of the hepatitis B virus (HBV), however it shares no sequence similarity with its helper virus and replicates independently in infected cells. HDV is the smallest human pathogenic RNA virus and shares numerous characteristics with viroids. Like viroids, HDV has a circular RNA genome which adopts a rod-like secondary structure, possesses ribozyme domains, replicates in the nucleus of infected cells by redirecting host DNA-dependent RNA polymerases (RNAP), and relies heavily on host proteins for its replication due to its small size and limited protein coding capacity. These similarities suggest an evolutionary relationship between HDV and viroids, and information on HDV could allow a better understanding of viroids and might globally help understanding the pathogenesis and molecular biology of these subviral RNAs. In this review, we discuss the host involvement in HDV replication and its implication for HDV pathogenesis.

Keywords: hepatitis delta virus; host–pathogen interaction; viral disruption of host processes.

Figure 1

Hepatitis delta virus genomic RNA, antigenomic RNA and mRNA. The delta ribozymes are represented by the green boxes on both strands and the cleavage sites are indicated by scissor symbols. The delta antigen (HDAg) open reading frame (ORF) is represented in the antigenome by the red box, the arrow on position 1630 indicates its transcription start site and the X in the ORF represents the ADAR-1 editing site at a location corresponding to the termination codon of HDAg-S.

Figure 2

Hepatitis delta virus (HDV) replication model: symmetrical rolling circle. HDV genomic strand (blue) is used as a template to generate the antigenomic RNA using a host polymerase to generate a multimeric linear strand. This strand is self-cleaved by endogenous delta ribozymes (scissor symbols) and presumably ligated by a host enzyme to form the antigenomic monomeric strand (pink). The same steps are repeated on the antigenomic strands to produce a newly synthesized genomic strand. The genomic template is also used for the antigen mRNA synthesis. Question marks next to several RNAPs indicate that the involvement in HDV biology remains controversial.