Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
PLoS One. 2010 Dec 28;5(12):e15139. doi: 10.1371/journal.pone.0015139.
The aim of the study was to analyze genotype I hepatitis A virus (HAV) 5' nontranslated region (NTR) sequences from a recent outbreak in South Korea and compare them with reported sequences from Japan. We collected a total of 54 acute hepatitis A patients' sera from HAV genotype I [27 severe disease (prothrombin time INR ≥ 1.50) and 27 mild hepatitis (prothrombin time INR <1.00)], performed nested RT-PCR of 5' NTR of HAV directly sequenced from PCR products (∼ 300 bp), and compared them with each other. We could detect HAV 5'NTR sequences in 19 of the 54 (35.1%) cases [12 of 27 severe cases (44.4%) and 7 of 27 self-limited cases (25.9%)], all of which were subgenotype IA. Sequence analysis revealed that sequences of severe disease had 93.6%-99.0% homology and of self-limited disease 94.3%-98.6% homology, compared to subgenotype IA HAV GBM wild-type IA sequence. In this study, confirmation of the 5'NTR sequence differences between severe disease and mild disease was not carried out. Comparison with Japanese HAV A10 revealed (222)C to G or T substitution in 8/12 cases of severe disease and (222)C to G or T and (392)G to A substitutions in 5/7 and 4/7 cases of mild disease, respectively, although the nucleotide sequences in this study showed high homology (93.6%-100%). In conclusion, HAV 5'NTR subgenotype IA from Korea had relatively high homology to Japanese sequences previously reported from Japan, and this region would be considered one of the antiviral targets. Further studies will be needed.
本研究旨在分析韩国近期爆发的甲型肝炎病毒（HAV）I 型 5'非翻译区（NTR）序列，并将其与日本报道的序列进行比较。我们收集了总共 54 例 HAV I 型急性肝炎患者的血清[27 例严重疾病（凝血酶原时间 INR ≥ 1.50）和 27 例轻度肝炎（凝血酶原时间 INR <1.00）]，直接从 PCR 产物中进行 HAV 5'NTR 的嵌套 RT-PCR，然后对其进行测序，并相互比较。我们在 54 例中的 19 例（35.1%）中检测到 HAV 5'NTR 序列[27 例严重病例中的 12 例（44.4%）和 27 例自限性病例中的 7 例（25.9%）]，所有这些均为亚基因型 IA。序列分析显示，严重疾病的序列与亚基因型 IA HAV GBM 野生型 IA 序列的同源性为 93.6%-99.0%，而自限性疾病的序列同源性为 94.3%-98.6%。在本研究中，并未对严重疾病和轻度疾病的 5'NTR 序列差异进行确认。与日本 HAV A10 的比较显示，严重疾病的 12 例中有 8 例（222）C 到 G 或 T 的取代，轻度疾病的 7 例中有 5 例（222）C 到 G 或 T 和（392）G 到 A 的取代，7 例中有 4 例（222）C 到 G 或 T 和（392）G 到 A 的取代，但本研究中的核苷酸序列显示出高度的同源性（93.6%-100%）。总之，韩国的 HAV 5'NTR 亚基因型 IA 与日本之前报道的日本序列具有较高的同源性，该区域将被视为抗病毒靶点之一。需要进一步研究。
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