Lechner S, Rispeter K, Meisel H, Kraas W, Jung G, Roggendorf M, Zibert A
Institut für Virologie, Universitätsklinikum, Essen, Germany.
Virology. 1998 Apr 10;243(2):313-21. doi: 10.1006/viro.1998.9069.
The relatively high variability of the hepatitis C virus (HCV) envelope proteins E1 and E2 suggests that parts of these proteins other than the hypervariable region 1 (HVR1) might be involved in the induction of virus neutralizing antibodies. To test this hypothesis, two HCV proteins, pE1 and pE2 delta, were generated by in vitro translation. They represent amino acids 174-337 of E1 and 411-688 of E2, respectively, of isolate HCV-AD78; the protein pE2 delta contained no HVR1. As a control, protein pG.HVR1, which represents amino acids 384-410 of HVR1 of isolate HCV-AD78, was expressed separately. These three proteins were used in an immunoprecipitation assay to detect the presence of antiviral antibodies in sera of patients infected with the same isolate of HCV (HCV-AD78). Sera were obtained 4-8 months postinfection from patients who later resolved an acute infection or developed chronic liver disease. A high prevalence of antibodies (up to 85.7%) against pE1 and pE2 delta could be detected in both groups of patients, suggesting that these forms of the HCV envelope proteins contain B-cell epitopes. The antibody responses against proteins pE1 and pE2 delta did not differ significantly between patients with resolving or chronic infection, whereas antibodies against protein pG.HVR1 were associated with resolution of infection. Rabbit antisera raised against pE1 and pE2 delta were tested for their ability to neutralize the binding of HCV to susceptible cells in tissue cultures. The results suggested that although a few B-cell epitopes outside of HVR1 can induce virus neutralizing antibodies, these antibodies are probably not associated with the resolution of infection.
丙型肝炎病毒（HCV）包膜蛋白E1和E2具有相对较高的变异性，这表明这些蛋白中除高变区1（HVR1）之外的部分可能参与病毒中和抗体的诱导。为了验证这一假设，通过体外翻译产生了两种HCV蛋白，即pE1和pE2δ。它们分别代表HCV-AD78分离株E1的第174 - 337位氨基酸和E2的第411 - 688位氨基酸；蛋白pE2δ不含HVR1。作为对照，单独表达了代表HCV-AD78分离株HVR1第384 - 410位氨基酸的蛋白pG.HVR1。这三种蛋白用于免疫沉淀试验，以检测感染同一HCV分离株（HCV-AD78）患者血清中抗病毒抗体的存在。在感染后4 - 8个月从后来清除急性感染或发展为慢性肝病的患者中获取血清。在两组患者中均检测到针对pE1和pE2δ的高抗体阳性率（高达85.7%），这表明这些形式的HCV包膜蛋白含有B细胞表位。清除感染或慢性感染患者针对蛋白pE1和pE2δ的抗体反应无显著差异，而针对蛋白pG.HVR1的抗体与感染清除相关。检测了针对pE1和pE2δ产生的兔抗血清在组织培养中中和HCV与易感细胞结合的能力。结果表明，尽管HVR1之外的一些B细胞表位可诱导病毒中和抗体，但这些抗体可能与感染清除无关。
