Characterization of a new genotype II hepatitis delta virus from Taiwan

Three genotypes of HDV, which may be associated with different clinical pictures and epidemiological patterns, have been identified. In contrast to Type I and Type III HDV, both of which have multiple isolates, Type II HDV so far includes only a single isolate (Japan-1) from a low prevalence area (Japan). Recently, Type II has been reported to be the predominant genotype in Taiwan, which is also a low prevalence area, and is associated with less aggresive disease than Type I. However, the sequence and structure of these viruses have not been characterized. The complete characterization of a second member (Taiwan-3 isolate) of the Type II HDV from Taiwan is reported. These two Type II HDV isolates (Taiwan-3 and Japan-1) have 93.8% nucleotide homology and 89.3% amino acid homology, respectively. These shared sequences establish the common characteristics of Type II viruses. Sequence comparisons of various HDV genotypes show that the autocatalytic region of the RNA is relatively conserved between Type I and Type II (88.5-95.6% homology) but is significantly divergent in Type III (76.8-80.3% homology). The hypervariable region (nucleotides 1602-658) of RNA, however, is heterogeneous (64.9-73.0%) among all three genotypes. The delta antigen sequence is also very heterogeneous (64.9-73.0%). Most strikingly, the C-terminal sequence (19 amino acids) of the large delta antigen is almost completely different in each of the three genotypes. The heterogeneity in this region of three HDV genotypes may be a basis for their different biological properties, and the nucleotide sequences of this region can be used to differentiate the different genotypes of HDV. The consensus sequence in the four previously identified conserved domains of HDV RNA is defined more precisely.