Analysis of specific immune response to HCV gene-transfected cells

HCV基因转染细胞的特异性免疫反应分析

• 批准号: 06670587
• 负责人: YAMAGUCHI Katsumi
• 金额: $ 1.34万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670587/
• 关键词: HCV; CTL; Gene transfection; C型肝炎ビールス

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.

摘要1) HCV高变区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的405位上含有Leu，并且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水平的重新升高，HCV又重新出现，并且该病毒在405位点发生了突变。这些结果表明该区域含有HCV感染的中和抗体所识别的免疫表位。2)HCV核心蛋白免疫表位的多重性。利用酶联免疫吸附测定(ELISA)，我们分析了HCV核心蛋白的免疫表位。 发现HCV衣壳蛋白内存在多个免疫反应性表位。其中，急性肝炎（AH）患者的优势表位位于SCP-4（氨基酸位置48至67）内，慢性肝炎（CH）患者的优势表位位于SCP-2（氨基酸位置19至31）和SCP-3（氨基酸位置30至49）内。 AH 中抗 SCP-2、-3 和 -4 的患病率分别为 45%、36% 和 73%，CH 中抗 SCP-2、-3 和 -4 的患病率分别为 76%、86% 和 57%。通过使用这些测定，我们估计了这些抗体在诊断 AH 或 CH 中的用途。这些结果表明，所有 7 名在不存在抗 SCP-4 的情况下具有抗 SCP-3 的患者均为 CH，而在不存在抗 SCP-3 的情况下具有抗 SCP-4 的 6 名患者中的 5 名是 AH。因此，这些结果表明这些抗 SCP（尤其是抗 SCP-3）的测量结果与 -4，可能为区分HCV急性和慢性感染提供一些可能性。

项目成果

H.Sekiya: "Genetic alteration of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis : humoral immune response to hyper variable region 1." Int.J.Cancer. 57. 664-670 (1994)

H.Sekiya：“丙型肝炎病毒从急性肝炎进展到复发阶段时假定的包膜蛋白编码区的基因改变：对高可变区 1 的体液免疫反应。”

N.Katoh: Hepatitis C virus hypervarible region may confer escape from immunosuveillance, in viral hepatitis and Liver disease (eds.Nishioka et al.). 329-333 (1994)

N.Katoh：丙型肝炎病毒高变区可能使病毒性肝炎和肝脏疾病逃避免疫监视（Nishioka 等人编）。

H. Sekiya: "Genetic alteration of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis : humoral immune response to hyper variable region 1." Int. J. Cancer. 57. 664-670 (1994)

H. Sekiya：“丙型肝炎病毒从急性肝炎进展到复发阶段时假定的包膜蛋白编码区的基因改变：对高可变区 1 的体液免疫反应。”

N. Katoh: "Hepatitis C virus hyervarible region may confer escape from immunosuveillance." viral hepatitis and Liver disease Ceds. Nishioka et al.,. 329-333 (1994)

N. Katoh：“丙型肝炎病毒高变区可能会逃避免疫监视。”

N. Katoh: "Hepatitis C virus hyervarible region may confer escape from immunosuveillance." Viral hepatitis and Liver disease(eds,Nishioka et al.). 329-333 (1994)

N. Katoh：“丙型肝炎病毒高变区可能会逃避免疫监视。”