Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 11, C1121ABG Buenos Aires, Argentina.
Laboratorio de Virología y Genética Molecular (LVGM), Facultad de Ciencias Naturales y Ciencias de la Salud Sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, Chubut, 9100 Trelew, Argentina.
Biomed Res Int. 2017;2017:1728456. doi: 10.1155/2017/1728456. Epub 2017 Nov 12.
High hepatitis C virus (HCV) genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1-) coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith's phylogenetic diversity (PD), which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.
高丙型肝炎病毒 (HCV) 遗传多样性影响传染性/致病性，影响与纤维化程度和肝细胞癌相关的慢性肝病进展。HCV 核心蛋白在细胞生长调节和宿主基因表达中起着重要作用。在人类免疫缺陷病毒 1 型 (HIV-1) 合并感染个体中，肝纤维化的加速机制尚不清楚。我们旨在研究在一组高度同质的干扰素治疗 HIV-HCV 合并感染患者中，明确的 HCV-1a 核心多态性和遗传异质性是否与纤维化有关。通过 Faith 的系统发育多样性 (PD) 来衡量遗传异质性，这在 HCV 中研究甚少。招募了 18 名在开始抗 HCV 治疗前表现出不同肝纤维化阶段的 HIV-HCV 合并感染患者。在基线和治疗期间及之后进行采样，最长达 72 周。在宿主间/宿主内水平，使用分子克隆和 Sanger 测序研究 HCV-1a 群体。获得了涵盖 HCV-1a 核心区域 573 位 C 的超过 400 个完整 HCV-1a 核心序列。以前在 HCV-1b 核心区域 70 和 91 位发现的氨基酸取代未观察到。然而，在轻度纤维化病例中 HCV 遗传异质性高于严重纤维化病例。这些结果表明 PD 作为与慢性丙型肝炎进展相关的病毒相关因素具有潜在的应用价值。这些观察结果应在更大的队列中进行重新评估，以证实我们的发现并评估其他潜在的协变量。
