Pawlotsky J M, Pellerin M, Bouvier M, Roudot-Thoraval F, Germanidis G, Bastie A, Darthuy F, Rémiré J, Soussy C J, Dhumeaux D
Department of Bacteriology and Virology, Hôpital Henri Mondor, Université Paris XII, Créteil, France.
J Med Virol. 1998 Apr;54(4):256-64.
HCV exists within its host as pools of related genetic variants referred to as quasispecies. The hypervariable region 1 (HVR1) of the E2 envelope gene is subjected to strong selective pressure from neutralizing antibodies. The genetic complexity of this region is defined as the total number of genetic variants within the quasispecies population. The genetic complexity of the HVR1 region was examined in patients with chronic hepatitis C and its relationship with the epidemiology of HCV infection, and its influence on liver disease and the response to interferon treatment were determined in 114 patients with chronic hepatitis C. The genetic complexity of the HVR1 major variants was measured before treatment by using a polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) technique, and was compared with epidemiological, clinical, virological and histological features. The patients were treated with 3 megaunits of interferon (IFN) alfa for 3 to 6 months and the response to treatment was assessed at 3, 6 and 12 months. The HVR1 could be studied in 101 of the 114 patients (89%). Genetic complexity was significantly higher in patients infected through blood transfusion than intravenous drug use (mean complexity index: 5.7 +/- 2.3 vs. 4.7 +/- 1.5, respectively; P = 0.04). This relationship was independent of age and the estimated time since infection. No significant relationship was found with other parameters of infection or liver disease. In univariate analysis, the genetic complexity of HVR1 major variants did not affect the rates of ALT normalization at months 3 and 6 of IFN treatment. HVR1 genetic complexity was lower in patients with a sustained virological response than in non-responders (4.0 +/- 1.7 vs. 5.4 +/- 2.0, respectively; P = 0.07). In multivariate analysis of pretreatment parameters associated with a sustained virological response to treatment, three parameters appeared to be independent predictors of such a response: a low viral load (P < 0.04), a low anti-HCV core IgM titer (P = 0.03) and a low genetic complexity of HVR1 major variants (P < 0.04). In conclusion, the HVR1 of HCV has a quasispecies distribution in infected individuals. Its genetic complexity is significantly higher in transfusion recipients than in intravenous drug users, suggesting that the size of the initial inoculum affects the later emergence and development of viral quasispecies. The genetic complexity of HVR1, together with viral load and the anti-HCV IgM titer, are independent predictors of a sustained virological response to IFN alfa in patients with chronic hepatitis.
丙型肝炎病毒（HCV）在其宿主内以被称为准种的相关基因变异体库的形式存在。E2包膜基因的高变区1（HVR1）受到来自中和抗体的强大选择压力。该区域的基因复杂性被定义为准种群体内基因变异体的总数。对114例慢性丙型肝炎患者的HVR1区域的基因复杂性进行了检测，并确定了其与HCV感染流行病学的关系，以及其对肝脏疾病和干扰素治疗反应的影响。在治疗前，采用聚合酶链反应（PCR）-单链构象多态性（SSCP）技术测量HVR1主要变异体的基因复杂性，并将其与流行病学、临床、病毒学和组织学特征进行比较。患者接受300万单位的α干扰素治疗3至6个月，并在3、6和12个月时评估治疗反应。114例患者中有101例（89%）的HVR1可进行研究。输血感染患者的基因复杂性显著高于静脉吸毒感染患者（平均复杂性指数分别为：5.7±2.3对4.7±1.5；P = 0.04）。这种关系独立于年龄和估计的感染时间。未发现与感染或肝脏疾病的其他参数有显著关系。在单变量分析中，HVR1主要变异体的基因复杂性在干扰素治疗的第3个月和第6个月时不影响ALT正常化率。持续病毒学应答患者的HVR1基因复杂性低于无应答者（分别为4.0±1.7对5.4±2.0；P = 0.07）。在对与治疗的持续病毒学应答相关的治疗前参数进行多变量分析时，三个参数似乎是这种应答的独立预测因素：低病毒载量（P < 0.04）、低抗-HCV核心IgM滴度（P = 0.03）和HVR1主要变异体的低基因复杂性（P < 0.04）。总之，HCV的HVR1在感染个体中具有准种分布。其基因复杂性在输血受者中显著高于静脉吸毒者，这表明初始接种物的大小影响病毒准种的后期出现和发展。HVR1的基因复杂性，连同病毒载量和抗-HCV IgM滴度，是慢性肝炎患者对α干扰素持续病毒学应答的独立预测因素。
