A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization
A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization
复制标题
高变区 1 准种在丙型肝炎病毒颗粒逃脱中和过程中的可能作用
作者：
M. Korenaga;K. Hino;Y. Katoh;Y. Yamaguchi;M. Okuda;K. Yoshioka;K. Okita
我们检测了12例慢性丙型肝炎患者的免疫和非免疫复合型丙型肝炎病毒（HCV）颗粒中高变区1（HVR1）准种的一系列变化，以阐明丙型肝炎病毒在感染过程中的遗传多样化使病毒逃避体液免疫反应的机制。采用差速浮选离心和免疫沉淀分离免疫复合物和非免疫复合物，并通过亚克隆和测序确定其HVR1准种。通过Western blotting检测两例患者血清中对应重组HVR1蛋白的特异性抗体。在大多数研究的患者中，HVR1准种在免疫和非免疫复合物中的分布随着时间的推移发生了显著变化。在7名患者中，各种HCV克隆依次从非免疫复合物转变为免疫复合物。在其中4个实验中，具有相似HVR1序列的一组克隆在非免疫复合物中保持优势，而序列与优势克隆明显不同的少数克隆从非免疫复合物转向免疫复合物。这些结果提示了HCV持续感染的机制，其中主要的HCV克隆通过产生相当不同的次要“诱饵”克隆来逃避抗HVR1抗体的中和，这些克隆可能优先被中和。
We examined serial changes in the hypervariable region 1(HVR1) quasispecies both in immune and nonimmune complexed hepatitis C virus (HCV) particles from 12 patients with chronic hepatitis C to elucidate the mechanism by which genetic diversification of HCV during the course of infection allows escape of virus from the humoural immune response. Immune and nonimmune complexes were separated by differential flotation centrifugation and immunoprecipitation, and their HVR1 quasispecies were determined by subcloning and sequencing. The presence of a specific antibody against a specific viral clone in serum was examined in two patients by Western blotting of the corresponding recombinant HVR1 protein. The distribution of HVR1 quasispecies in both immune and nonimmune complexes conspicuously changed over time in most of the patients studied. In seven patients, various HCV clones serially shifted from nonimmune complexes to immune complexes. In four of them, a group of clones with similar HVR1 sequences to each other remained predominant in nonimmune complexes, whereas minor clones with sequences considerably divergent from the predominant clones shifted from nonimmune complexes to immune complexes. These results suggest a mechanism for persistent infection of HCV, in which major HCV clones escape from neutralization by anti‐HVR1 antibodies by generating considerably divergent minor ‘decoy’ clones which may be preferentially neutralized.