CHARACTERIZATION OF A NEW GENOTYPE-II HEPATITIS-DELTA VIRUS FROM TAIWAN

Three genotypes of HDV, which may be associated with different clinica l pictures and epidemiological patterns, have been identified. In cont rast 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 lo w prevalence area (Japan). Recently, Type II has been reported to be t he 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 characterize d. The complete characterization of a second member (Taiwan-3 isolate) of the Type II HDV from Taiwan is reported. These two Type II HDV iso lates (Taiwan-3 and Japan-1) have 93.8% nucleotide homology and 89.3% amino acid homology, respectively. These shared sequences establish th e common characteristics of Type II viruses. Sequence comparisons of v arious 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 hetero geneous (64.9-73.0%) among all three genotypes. The delta antigen sequ ence is also very heterogeneous (64.9-73.0%). Most strikingly, the C-t erminal sequence (19 amino acids) of the large delta antigen is almost completely different in each of the three genotypes. The heterogeneit y in this region of three HDV genotypes may be a basis for their diffe rent biological properties, and the nucleotide sequences of this regio n can be used to differentiate the different genotypes of HDV. The con sensus sequence in the four previously identified conserved domains of HDV RNA is defined more precisely. (C) 1996 Wiley-Liss, Inc.