No abstract

Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for transmission and propagation andinfects nearly 20 million people worldwide. The HDV genome is a compact circular single-stranded RNA genome with extensive intramolecular complementarity. Despite its different epidemiological and pathological patterns, the variability and geographical distribution of HDV are limited to three genotypes and two subtypes that have been characterized to date. Phylogenetic reconstructions based on the delta antigen gene and full-length genome sequence data show an extensive and probably ancient radiation of African lineages, suggesting that the genetic variability of HDV is much more complex than was previously thought, with evidence of additional clades. These results relate the geographic distribution of HDV more closely to the genetic variability of its helper HBV.Hepatitis D virus (HDV) is a transmissible agent discovered 26 years ago (30) that requires helper functions from the hepatitis B virus (HBV) for virion assembly and propagation (37). Thus, HDV infection is necessarily associated with HBV infection because HDV ribonucleoprotein buds through the hepatitis B surface antigen (HBsAg) excretory pathway. The HDV genome is a circular single-stranded RNA genome of approximately 1,680 bases with extensive intramolecular complementarity (41). Part of the HDV genome might have historical homology to viroids or plant virus satellite RNA sequences (10, 15), and a rolling-circle model has been developed for viral RNA replication (reviewed in reference 39). However, in contrast to viroids, which do not code for any protein, the HDV antigenome contains an open reading frame that was probably acquired by HDV from a cellular ancestor transcript, leading to the expression of the delta protein (1,20). Indeed, HDV mRNA is translated to sHD and LHD proteins, corresponding respectively to the "small-p24" and the "large-p27" hepatitis Delta proteins. The LHD amino acid sequence is identical to sHD with the addition of a carboxy-terminal extension of 19 to 20 amino acids following the editing of the sHD stop codon during the viral RNA replication cycle (23,43). sHD is required for viral replication and might promote RNA polymerase II elongation of nascent HDV RNA (45), while LHD is essential for HDV particle assembly (5).