Analysis of specific immune response to HCV gene-transfected cells

1）HCV高变区1的核苷酸序列在感染后的几个月内发生改变。我们发现原始HCV在HCV基因组HVR 1（野生型）的405位含有Leu，并且该病毒被同时出现的抗gp-70（抗HVR-1肽）清除。但随着血清ALT水平的再次升高，HCV再次出现，且该病毒存在405位突变。2）丙型肝炎病毒核心蛋白免疫表位的多样性用酶联免疫吸附试验（ELISA）检测发现，在丙型肝炎病毒衣壳蛋白中存在多个免疫反应性表位，其中，在急性肝炎（AH）患者中，优势表位位于SCP-4（氨基酸位置48至67）内，在慢性肝炎（CH）患者中，优势表位位于SCP-2（氨基酸位置19至31）和SCP-3（氨基酸位置30至49）内。抗SCP-2、-3和-4在AH和CH中的检出率分别为45%、36%和73%，而在CH中分别为76%、86%和57%。通过使用这些测定，我们估计了这些抗体用于诊断AH或CH的利用率。这些结果表明，所有7名具有抗SCP-3但不存在抗SCP-4的患者均为CH，6名具有抗SCP-4但不存在抗SCP-3的患者中有5名为AH。因此，这些结果表明，这些抗SCP，特别是抗SCP-3和-4，为区分HCV的急、慢性感染提供了可能。

Summary1) The nucleotide sequences of hypervarible region 1 of HCVundergoes alteration during the several months after the HCV infection. We found that the original HCV contains a Leu at position 405 in HVR1 of HCV genome (wild type) and that this virus was cleared with the simultaneously appeared anti-gp-70 (anti-HVR-1 peptide). However, with the re-elevation of serum ALT level, HCV was reappeared and this virus had the mutation of the position 405. These results suggest that this region contain the immunological epitope for being recognized by the neutralizing antibody for HCV infection.2) Multiplicity of the immunolgical epitopes of HCV core protein.Using the enzyme-linked immunosorbent assay (ELISA), we found that several immunoreactive epitopes exist within the capsid protein of HCV.Among of them, dominant epitopes were located within SCP-4 (amino acid positions 48 to 67) in acute hepatitis (AH) patients and within both SCP-2 (amino acid positions 19 to 31) and SCP-3 (amino acid positions 30 to 49) in chronic hepatitis (CH) patients. The prevalence of anti-SCP-2, -3, and -4 was 45%, 36% and 73% in AH and 76%, 86% and 57% in CH,respectively. By using these assays, we estimated the utilization of these antibodies for the diagnosis of either AH or CH.These results showed that all seven patients having anti-SCP-3 in the absence of anti-SCP-4 were CH and five of six having anti-SCP-4 in the absence of anti-SCP-3 were AH.Thus, these results indicate that the measurement of these anti-SCPs, and in particular anti-SCP-3 and -4, may provide some possibility for distinguishing acute and chronic infections of HCV.