Sakuma I, Enomoto N, Kurosaki M, Marumo F, Sato C
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Arch Virol. 1996;141(10):1921-32. doi: 10.1007/BF01718204.
Preliminary studies have shown that hepatitis C virus (HCV) quasispecies populations after interferon therapy are different from those before interferon, suggesting that selection of HCV quasispecies occurs during IFN treatment. To confirm this, fluctuations of HCV quasispecies populations were investigated by single strand conformation polymorphism analysis in eight patients who remained viremic during interferon treatment. In all patients, HCV quasispecies populations changed in 1 to 4 months after the start of interferon therapy. In seven patients, a minor population of HCV quasispecies that was present before the interferon therapy was selected and became predominant during the therapy, whereas the abundance of the other quasispecies was reduced. In the other patients, new HCV quasispecies that had not been detected before interferon therapy appeared and replaced the pretreatment HCV. In contrast, no significant changes were observed during the pretreatment period in these patients. In two patients, deduced amino acid sequences of the hypervariable region were identical despite the difference in nucleotide sequences between interferon-sensitive and interferon-resistant HCV. Thus, selection of HCV quasispecies occurs during interferon treatment and immune responses to the hypervariable region may not be the determining factor of the selection.
初步研究表明，干扰素治疗后的丙型肝炎病毒（HCV）准种群体与干扰素治疗前不同，这表明HCV准种的选择发生在干扰素治疗期间。为证实这一点，通过单链构象多态性分析对8例在干扰素治疗期间仍有病毒血症的患者的HCV准种群体波动情况进行了研究。在所有患者中，HCV准种群体在干扰素治疗开始后的1至4个月内发生了变化。在7例患者中，干扰素治疗前存在的一小部分HCV准种被选择并在治疗期间成为优势群体，而其他准种的丰度则降低。在另一名患者中，干扰素治疗前未检测到的新HCV准种出现并取代了治疗前的HCV。相比之下，这些患者在治疗前期未观察到显著变化。在两名患者中，尽管对干扰素敏感和耐药的HCV之间核苷酸序列存在差异，但高变区的推导氨基酸序列是相同的。因此，HCV准种的选择发生在干扰素治疗期间，并且对高变区的免疫反应可能不是选择的决定性因素。
