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丙型肝炎病毒相关疾病中针对丙型肝炎病毒NS4蛋白一个表位的免疫反应。

Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders.

作者信息

Longombardo G, Ferri C, Marchi S, Costa F, Lombardini F, Vacri L, Bombardieri S, Migliorini P

机构信息

Clinical Immunology and Rheumatology Unit, University of Pisa, Italy.

出版信息

Clin Immunol Immunopathol. 1998 May;87(2):124-9. doi: 10.1006/clin.1997.4498.

DOI:10.1006/clin.1997.4498
PMID:9614926
Abstract

NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.

摘要

NS4是丙型肝炎病毒(HCV)的一种非结构蛋白,是受感染个体中抗体的常见靶点。根据最近的数据,抗体经常识别NS4蛋白的1921 - 40序列。这项工作的目的是分析在不同HCV相关疾病中抗体与1921 - 40序列的反应性。尽管该序列位于病毒基因组的一个相对保守区域,但仍描述了两个菌株特异性序列。因此,合成了三种NS4 1921 - 1940肽:大多数病毒株共有的BK肽、J6(2a株)和J8(2b株)。这些肽在固相ELISA试验中用作抗原,以检测血清IgG抗体。在自身免疫性肝炎(AIH)患者的64%血清、慢性丙型肝炎(CHC)患者的51%血清和混合性冷球蛋白血症(MC)患者的22%血清中检测到与1921 - 40 BK肽反应的抗体。MC患者中阳性血清的频率显著低于AIH(P < 0.0001)或CHC(P < 0.0021)。用J6和J8肽也得到了类似结果。所有不与BK肽反应的血清对J6和J8均为阴性,相反,大多数与BK肽反应的血清也与J6和J8肽结合。未发现感染病毒的基因型与针对任何NS4肽的抗体存在之间存在相关性。这些结果表明,许多HCV感染个体产生针对NS4 1921 - 40序列的抗体。对该序列的免疫反应不是菌株特异性的,并且因与HCV感染相关的不同疾病而异。

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Clin Diagn Lab Immunol. 1999 Mar;6(2):279-81. doi: 10.1128/CDLI.6.2.279-281.1999.
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Clin Rev Allergy Immunol. 1998 Fall;16(3):249-64. doi: 10.1007/BF02737635.