Hofgärtner W T, Polyak S J, Sullivan D G, Carithers R L, Gretch D R
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, USA.
J Med Virol. 1997 Oct;53(2):118-26. doi: 10.1002/(sici)1096-9071(199710)53:2<118::aid-jmv3>3.0.co;2-c.
Previous studies from Japan have described an association between a conserved sequence within the hepatitis C virus (HCV) genome and resistance to interferon (IFN) therapy for patients infected with HCV genotype 1b [Enomoto et al. (1995): Journal of Clinical Investigation 96: 224-230; Enomoto et al. (1996): New England Journal of Medicine 334:77-81]. The present study examines amino acid sequences surrounding the putative Interferon Sensitivity Determining Region (ISDR) of the NS5A gene of HCV in 21 North American patients with genotype 1a or 1b infection receiving recombinant IFN therapy. The ISDR consensus or intermediate pattern was observed in 13 of 14 NS5A clones from North American patients infected with genotype 1b. However, we found no evidence of the consensus ISDR sequence in any NS5A clones isolated from 15 patients with genotype 1a infection. In select cases, gel shift analysis showed no significant changes in the clonal frequency of the putative ISDR domain of HCV genotype 1a or 1b infected patients who were either nonresponsive to IFN therapy, or relapsed following withdrawal of IFN therapy. These results suggest that a conserved ISDR domain is neither associated with, nor responsible for, IFN resistance in North American patients infected with HCV genotype 1a, and demonstrate a need for further investigation into the reported association between ISDR consensus sequences and IFN resistance in genotype 1b clones.
日本此前的研究描述了丙型肝炎病毒（HCV）基因组内一个保守序列与感染HCV 1b基因型患者对干扰素（IFN）治疗的耐药性之间的关联[榎本等人（1995年）：《临床研究杂志》96：224 - 230；榎本等人（1996年）：《新英格兰医学杂志》334：77 - 81]。本研究检测了21名接受重组IFN治疗的北美1a或1b基因型感染患者中，HCV NS5A基因假定的干扰素敏感性决定区域（ISDR）周围的氨基酸序列。在14个来自感染1b基因型的北美患者的NS5A克隆中，有13个观察到ISDR共有序列或中间模式。然而，我们在从15名1a基因型感染患者分离的任何NS5A克隆中均未发现共有ISDR序列的证据。在特定病例中，凝胶迁移分析显示，对IFN治疗无反应或在停止IFN治疗后复发的HCV 1a或1b基因型感染患者，其假定的ISDR结构域的克隆频率无显著变化。这些结果表明，在北美感染HCV 1a基因型的患者中，一个保守的ISDR结构域既不与IFN耐药性相关，也不是其原因，并表明需要进一步研究报道的1b基因型克隆中ISDR共有序列与IFN耐药性之间的关联。
