Hepatitis delta virus RNA replication

Abstract

Hepatitis delta virus (HDV) is a distant relative of plant viroids in the animal world. Similar to plant viroids, HDV replicates its circular RNA genome using a double rolling-circle mechanism. Nevertheless, the production of hepatitis delta antigen (HDAg), which is indispensible for HDV replication, is a unique feature distinct from plant viroids, which do not encode any protein. Here the HDV RNA replication cycle is reviewed, with emphasis on the function of HDAg in modulating RNA replication and the nature of the enzyme involved.

Keywords: RNA polymerases; RNA replication; RNA-dependent RNA synthesis; hepatitis delta antigen; hepatitis delta virus.

Figure 1.

Schematic diagrams of the structure of HDV RNAs. The antigenomic RNA and HDAg-encoding mRNA are detected only in the cells. The nucleotide numbers are according to Makino et al. [24] and represented in genomic orientation on both the genomic and antigenomic strands. The genomic RNA is represented in clockwise orientation, while the antigenomic RNA and HDAg-encoding mRNA are counterclockwise. Nucleotides 688/689 and 903/904 are ribozyme cleavage sites for genomic and antigenomic RNAs, respectively. The hatched boxes represent the ribozyme domains. Nucleotides 1015 (Ed) denotes RNA editing site. (A)_n represents polyadenylation signal.

Figure 2.

The functional domains and sites of posttranslational modifications of HDAg. RBD, RNA-binding domain; CCD, coiled-coil domain; NLS, nuclear localization signal; HLH, helix-loop-helix motif; PGRS proline/glysine-rich sequence; VAS, virus assembly signal; M, methylation; A, acetylation; P, phosphorylation; Pr, prenylation.