Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease.
We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (P=0.0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.
Watanabe
Hideki
H
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Nagayama
Kazuyoshi
K
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Enomoto
Nobuyuki
N
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Chinzei
Ryoko
R
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Yamashiro
Tsuyoshi
T
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Izumi
Namiki
N
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Yatsuhashi
Hiroshi
H
Institute for Clinical Research, World Health Organization Collaborating Center for Reference and Research on Viral Hepatitis, National Nagasaki Medical Center, Nagasaki, Japan.
Nakano
Tatsunori
T
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, USA.
Robertson
Betty H
BH
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, USA.
Nakasone
Hiroki
H
First Department of Internal Medicine, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Sakugawa
Hiroshi
H
First Department of Internal Medicine, School of Medicine, University of the Ryukyus, Okinawa, Japan.
Watanabe
Mamoru
M
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D016384:Consensus Sequence; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D019701:Hepatitis D, Chronic / Q000175:diagnosis* / Q000473:pathology; D003698:Hepatitis Delta Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D035923:Hepatitis delta Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
D035923:Hepatitis delta Antigens