Watanabe Hideki, Nagayama Kazuyoshi, Enomoto Nobuyuki, Chinzei Ryoko, Yamashiro Tsuyoshi, Izumi Namiki, Yatsuhashi Hiroshi, Nakano Tatsunori, Robertson Betty H, Nakasone Hiroki, Sakugawa Hiroshi, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
J Gen Virol. 2003 Dec;84(Pt 12):3275-3289. doi: 10.1099/vir.0.19499-0.
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.
我们测定了40例日本患者的丁型肝炎病毒（HDV）基因组序列，其中大多数患者来自日本冲绳的宫古岛。通过直接对4个部分重叠的PCR产物进行测序，确定了40例患者中33个HDV全基因组的一致序列。系统发育树分析将这33个完整的HDV基因组分为HDV基因型I（2例患者）、基因型IIa（1例患者）和基因型IIb（30例患者）。在30例基因型IIb患者中，存在两个遗传变异簇。一组由6个分离株组成，与之前台湾报道的基因型IIb具有显著同源性。另一组由24个分离株组成，其序列形成了一个新的遗传亚组（基因型IIb-宫古岛；IIb-M）。当详细比较IIb和IIb-M的遗传结构时，在赋予大丁型抗原包装信号的C末端序列以及RNA编辑位点发现了特征性变异。在总共37例患者中确定基因型IIb的亚类，包括7例HDV部分序列已确定的患者，结果显示8例为IIb型，29例为IIb-M型。尽管两组之间乙型肝炎病毒的临床背景或病毒学状态没有显著差异，但基因型IIb-M的患者比基因型IIb的患者慢性肝炎和肝硬化的进展更严重（P=0.0009）。这些数据表明存在HDV基因型IIb的一个遗传亚组，其与不同的临床特征相关，并且可能与HDV基因组功能重要部分的遗传变异有关。
