Kurosaki M, Enomoto N, Sakamoto N, Tanaka Y, Tang L, Hoshino Y, Izumi N, Marumo F, Sato C
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
J Hepatol. 1995 May;22(5):527-35. doi: 10.1016/0168-8278(95)80446-3.
Although persistent hepatitis C virus infection is closely associated with the development of hepatocellular carcinoma, the nature of hepatitis C virus replication in the hepatocellular carcinoma tissue has not been fully characterized. To study this, carcinoma and non-carcinoma tissues were obtained from five patients with hepatocellular carcinoma. Total RNA was recovered from each tissue, and a portion of the envelope gene of replicating hepatitis C virus was amplified by minus-strand-specific reverse transcription and nested polymerase chain reaction. The amplified cDNA was examined by single strand conformation polymorphism analysis and sequencing. Hepatitis C virus replication was detected in both carcinoma and non-carcinoma tissues in four patients who were positive for serum hepatitis C virus markers. In one patient, a single species with identical envelope 2 genome was obtained from both carcinoma and non-carcinoma tissues. In the other three patients, the replicating hepatitis C virus existed as a mixture of 2-5 species with different but highly homologous (82-99%) envelope 2 genomes (quasispecies populations). The constitution of viral populations was different between carcinoma and non-carcinoma tissues. A total of ten sequences were recovered; four sequences were found in both tissues, two were found in carcinoma tissues, and four were found in non-carcinoma tissues. The difference in the constitution of quasispecies populations between carcinoma and non-carcinoma tissues confirms the unequivocal replication of hepatitis C virus in both tissues, and may imply the presence of different biological properties among hepatitis C virus with different sequences.
尽管丙型肝炎病毒持续感染与肝细胞癌的发生密切相关，但丙型肝炎病毒在肝细胞癌组织中的复制特性尚未完全明确。为研究这一问题，从5例肝细胞癌患者获取癌组织和非癌组织。从每个组织中提取总RNA，通过负链特异性逆转录和巢式聚合酶链反应扩增复制中的丙型肝炎病毒包膜基因的一部分。对扩增的cDNA进行单链构象多态性分析和测序。在血清丙型肝炎病毒标志物阳性的4例患者的癌组织和非癌组织中均检测到丙型肝炎病毒复制。在1例患者中，从癌组织和非癌组织中均获得了具有相同包膜2基因组的单一病毒株。在其他3例患者中，复制中的丙型肝炎病毒以2 - 5种具有不同但高度同源（82 - 99%）包膜2基因组的病毒株混合物形式存在（准种群体）。癌组织和非癌组织中病毒群体的构成不同。共获得10个序列；4个序列在两种组织中均有发现，2个在癌组织中发现，4个在非癌组织中发现。癌组织和非癌组织中准种群体构成的差异证实了丙型肝炎病毒在两种组织中均有明确复制，并且可能意味着不同序列的丙型肝炎病毒具有不同的生物学特性。
