Departments of Laboratory Medicine, University of Washington, Seattle, WA 98104, USA.
J Infect Dis. 2010 Mar 15;201(6):912-22. doi: 10.1086/650699.
The hepatitis C virus (HCV) core protein is implicated in diverse aspects of HCV-induced pathogenesis. There is a paucity of information on core in acute hepatitis C infection.
We analyzed core gene sequences and protein functions from 13 patients acutely infected with HCV genotype 1.
Although core isolates differed slightly between patients, core quasispecies were relatively homogeneous within each patient. In 2 of 4 patients studied temporally, core quasispecies did not change over time. Comparison with more than 2700 published core isolates indicated that amino acid changes from a prototype reference strain found in acute core isolates were present in chronically infected persons at low frequency (6.4%; range, 0%-32%). Core isolates associated with lipid droplets to similar degrees in Huh7 cells. Core diffusion in cells was not affected by nonconservative changes F130L and G161S in the lipid targeting domain of core. Core isolates inhibited interferon-stimulated response element- and nuclear factor kappaB-dependent transcription and tumor necrosis factor alpha-induced nuclear translocation of nuclear factor kappaB and were also secreted from Huh7 cells.
The data suggest that upon transmission, core quasispecies undergo genetic homogenization associated with amino acid changes that are rarely found in chronic infection and that, despite genetic variation, acute core isolates retain similar functions in vitro.
丙型肝炎病毒（HCV）核心蛋白与 HCV 诱导发病机制的多个方面有关。关于急性丙型肝炎感染中的核心蛋白，信息很少。
我们分析了 13 例急性 HCV 基因 1 型感染患者的核心基因序列和蛋白功能。
尽管患者之间的核心分离株略有不同，但每个患者的核心准种相对均一。在 4 例患者中，有 2 例在时间上进行了研究，核心准种没有随时间变化。与 2700 多个已发表的核心分离株相比，急性核心分离株中发现的原型参考株的氨基酸变化在慢性感染人群中的频率较低（6.4%；范围，0%-32%）。核心分离株在 Huh7 细胞中与脂滴的结合程度相似。非保守性改变 F130L 和 G161S 不会影响细胞内核心的扩散，这两个改变位于核心的脂质靶向结构域。核心分离株抑制干扰素刺激反应元件和核因子 kappaB 依赖性转录以及肿瘤坏死因子 alpha 诱导的核因子 kappaB 核转位，并且也从 Huh7 细胞中分泌。
这些数据表明，在传播过程中，核心准种发生遗传同质化，伴随着在慢性感染中很少发现的氨基酸变化，尽管存在遗传变异，但急性核心分离株在体外仍保留相似的功能。
