School of Molecular & Cellular Biology & Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire LS2 9JT, United Kingdom.
Virology. 2014 Jan 5;448:117-24. doi: 10.1016/j.virol.2013.10.003. Epub 2013 Oct 24.
Secreted infectious particles generated by the genotype 2a JFH-1 hepatitis C virus infectious clone are resistant to acidic pH, whereas intracellular virions remain acid-labile. Thus, JFH-1 particles are thought to undergo pH maturation as they are secreted from the cell. Here, we demonstrate that both infectious intracellular and secreted genotype 1a (H77)/JFH-1 chimaeric particles display enhanced acid sensitivity compared with JFH-1, although pH maturation still occurs upon release. Introduction of p7 sequences from genotype 1a infected HCV patients into the H77/JFH-1 background yielded variable effects on infectious particle production and sensitivity to small molecule inhibitors. However, two selected patient p7 sequences increased the acid stability of secreted, but not intracellular H77/JFH-1 particles, suggesting that p7 directly influences particle pH maturation via an as yet undefined mechanism. We propose that HCV particles vary in acid stability, and that this may be dictated by variations in both canonical structural proteins and p7.
由基因型 2a JFH-1 丙型肝炎病毒感染性克隆产生的分泌性感染性颗粒对酸性 pH 具有抗性，而细胞内病毒仍对酸性敏感。因此，人们认为 JFH-1 颗粒在从细胞中分泌时会经历 pH 成熟。在这里，我们证明，与 JFH-1 相比，感染性细胞内和分泌的基因型 1a（H77）/JFH-1 嵌合颗粒均显示出增强的酸性敏感性，尽管在释放时仍会发生 pH 成熟。将来自感染 HCV 患者的基因型 1a 的 p7 序列引入 H77/JFH-1 背景中，对感染性颗粒的产生和对小分子抑制剂的敏感性产生了不同的影响。然而，两种选定的患者 p7 序列增加了分泌的，但不是细胞内的 H77/JFH-1 颗粒的酸性稳定性，这表明 p7 通过尚未确定的机制直接影响颗粒的 pH 成熟。我们提出 HCV 颗粒在酸性稳定性方面存在差异，这可能是由规范的结构蛋白和 p7 的变化决定的。
