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).

Currently, three genotypes of hepatitis delta virus (HDV) are described. The most common, genotype I, has a worldwide distribution ; in contrast, genotype II has been found previously only in Japan and Taiwan, while genotype III is found exclusively in South America. Considering the high prevalence of HDV in Northern Siberia (Russia), restriction fragment length polymorphism (RFLP) was used to analyse HDV genotypes from 29 infected patients living in Yakutia. Of these isolates, 11 were characterized by partial nucleotide sequencing and two isolates were completely sequenced. Phylogenetic inference methods included maximum parsimony, maximum likelihood and distance analyses. A restriction pattern consistent with HDV genotype I was found in 14 samples, while the remaining 15 showed a different restriction pattern, inconsistent with any known genotype. Five Yakutian HDV isolates with the type I restriction pattern were sequenced and confirmed to be affiliated with genotype I, although the phylogenetic results indicate that they were heterogeneous and did not cluster together. Sequencing of eight isolates with the new RFLP pattern revealed that these isolates were most closely related to HDV genotype II. In contrast to HDV Yakutian genotype I sequences, all of these type II sequences formed a well-defined clade on phylogenetic trees. Comparison of clinical presentations during hospitalization between patients infected with HDV type I (n l 14) and type II (n l 15) did not reveal any differences in the severity of infection. These data indicate that the distribution of genotype II is not restricted to Taiwan or Japan, but spreads over Northern Asia, appearing in the native population of Yakutia. Type II Yakutian strains appeared to form a well-defined subclade and could be associated with severe chronic hepatitis in this area.

In this study, we analyze self-reported development experience of adolescents involved in various