Polyak S J, Faulkner G, Carithers R L, Corey L, Gretch D R
Department of Laboratory Medicine, University of Washington Medical Center, Seattle 98144, USA.
J Infect Dis. 1997 May;175(5):1101-7. doi: 10.1086/516448.
Hepatitis C virus (HCV) quasispecies heterogeneity was assessed in pretreatment sera of 22 patients treated with interferon (IFN). Quasispecies heterogeneity was quantitated by analysis of 490 hypervariable region 1 (HVR1) clones using gel shift analysis (GSA), which allowed determination of two components of HCV quasispecies heterogeneity: genetic complexity (number of variants) and genetic diversity (mean genetic distance between variants). HCV genotype and pretreatment RNA titer were similar between responders (n = 12) and nonresponders (n = 10). GSA correlated well with nucleotide sequencing for estimating HCV genetic diversity (R = .952; P < .001). A positive correlation of .666 (P < .001) was observed between genetic diversity and complexity, suggesting that these components of quasispecies heterogeneity were related. However, while there were no significant differences in pretreatment complexity or genetic diversity among response groups, higher pretreatment genetic diversity was predictive of response failure (P = .041). Assessment of HVR1 heterogeneity by GSA revealed important relationships between quasispecies genetic diversity, complexity, and response to IFN therapy and suggested a need for analysis of other HCV genes.
在接受干扰素（IFN）治疗的22例患者的治疗前血清中评估了丙型肝炎病毒（HCV）准种的异质性。通过使用凝胶迁移分析（GSA）分析490个高变区1（HVR1）克隆来定量准种异质性，该分析可确定HCV准种异质性的两个组成部分：遗传复杂性（变异体数量）和遗传多样性（变异体之间的平均遗传距离）。应答者（n = 12）和无应答者（n = 10）之间的HCV基因型和治疗前RNA滴度相似。GSA与核苷酸测序在估计HCV遗传多样性方面具有良好的相关性（R = 0.952；P <0.001）。在遗传多样性和复杂性之间观察到0.666的正相关性（P <0.001），表明准种异质性的这些组成部分是相关的。然而，虽然应答组之间治疗前的复杂性或遗传多样性没有显著差异，但较高的治疗前遗传多样性可预测应答失败（P = 0.041）。通过GSA评估HVR1异质性揭示了准种遗传多样性、复杂性与IFN治疗应答之间的重要关系，并表明需要分析其他HCV基因。
