Analysis of specific immune response to HCV gene-transfected cells

1) HCV高可变区1的核苷酸序列在HCV感染后的几个月内发生改变。我们发现原始HCV在HCV基因组（野生型）HVR1第405位含有一个Leu，该病毒被同时出现的抗gp-70（抗hvr -1肽）清除。然而，随着血清ALT水平的再次升高，HCV再次出现，该病毒发生405位点突变。这些结果表明，该区域含有HCV感染中和抗体识别的免疫表位。2) HCV核心蛋白免疫表位的多样性。利用酶联免疫吸附试验（ELISA），我们发现HCV衣壳蛋白中存在几个免疫反应性表位。其中，优势表位位于急性肝炎（AH）患者的SCP-4（氨基酸位置48 ~ 67）内，以及慢性肝炎（CH）患者的SCP-2（氨基酸位置19 ~ 31）和SCP-3（氨基酸位置30 ~ 49）内。AH中抗scp -2、-3和-4的患病率分别为45%、36%和73%，CH中分别为76%、86%和57%。通过这些试验，我们估计了这些抗体在AH或CH诊断中的应用。结果表明，在没有抗scp -4的情况下，所有7例有抗scp -3的患者都是CH，而在没有抗scp -3的情况下，6例有抗scp -4的患者中有5例是AH。因此，这些结果表明，检测这些抗scp -3，特别是抗scp -3和-4，可能为区分急性和慢性HCV感染提供一些可能性。

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.