Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment.
Antibodies in human sera specific to hypervariable region 1 of hepatitis C virus can block viral attachment.
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人类血清中针对丙型肝炎病毒高变区 1 的抗体可以阻止病毒附着。
作者：
Andree Zibert;Eckart Schreier;Michael Roggendorf
据推测，特异于丙型肝炎病毒（HCV）的推定包膜蛋白E2内的高变区1（HVR 1）的抗体可以中和病毒。我们研究了在单一来源爆发中被污染的抗D免疫球蛋白制剂（HCV-AD 78）感染的患者血清中的此类抗体。测定了HCV-AD 78高变区1（HVR 1）的cDNA序列。四种主要变体（HVR 1. A、B、C和D）在大肠杆菌中表达为融合蛋白。67%的血清含有HVR1.A抗体。与暴发感染无关的血清也识别HVR1.A，但程度较低（15%），表明并非所有HVR 1特异性抗体都是绝对分离特异性的。在感染后早期（p.i.）（<或= 1年），但也在几年后获得的血清中。采用HCV与组织培养细胞的体外结合试验进一步表征这些血清。在早期p.i.防止HCV与细胞结合。这种血清与HVR 1特异性融合蛋白的预孵育恢复了5个血清中的4个中HCV与细胞的结合。这些发现表明大多数中和抗体针对HVR 1。
It has been postulated that antibodies specific to the hypervariable region 1 (HVR1) within the putative envelop protein E2 of hepatitis C virus (HCV) can neutralize virus. We studied such antibodies in sera of patients who were infected in a single-source outbreak by a contaminated anti-D immunoglobulin preparation (HCV-AD78). The nucleotide sequences of cDNAs encoding HVR1 of HCV-AD78 were determined. The four major variants (HVR1.A, B, C, and D) were expressed as fusion proteins in Escherichia coli. Sixty-seven percent of sera contained antibodies to HVR1.A. Sera unrelated to infection of the outbreak also recognized HVR1.A but to a lesser extent (15%), suggesting that not all HVR1-specific antibodies are absolutely isolate-specific. Antibodies directed against individual variants of HVR1 were found in sera obtained early postinfection (p.i.) (< or = 1 year) but also in sera obtained several years later. An in vitro binding assay of HCV to tissue culture cells was employed to further characterize these sera. Five of seven sera that were obtained early p.i. prevented binding of HCV to cells. Preincubation of such sera with HVR1-specific fusion proteins restored binding of HCV to cells in four of five sera. These findings suggest that the majority of neutralizing antibodies are directed against HVR1.