Replication strategy and pathogenesis of HDV

Abstract

Hepatitis delta virus (HDV) is a defective human pathogen which is dependent on hepatitis B virus (HBV) for replication and expression. The full extent of the helper function is still unknown, but HBV provides a hepatitis B surface antigen envelope that surrounds teh HDV-specific internal components of the HDV virion. These components are a circular single-stranded RNA genome of approximately 1.7kb and hepatitis delta antigen (HDAg). The genome has five potential genes, but a protein product (HDAg) has only been identified from one. HDAg is found in the liver and serum of infected individuals as two related polypeptides of 24- and 27-kDa. The genome also shares a number of similarities with the viroids, highly pathogenic agents of plants including (1) the ability for RNA self-cleavage in vitro ; (2) genome replication by the rolling circle mechanism; (3) nuclear replication by host cell RNA polymerase II. A number of studies have shown that HDV RNA replication is dependent on HDAg; however recent evidence suggests that the role of HDAg is to transport HDV RNA to the nucleus but it does not form part of the transcriptional complex per se . Virus replication is generally associated with cell death, both in vivo and in vitro , that may be a result of the expression of HDAg p24 which appears to inhibit host cell RNA synthesis.