DIAGNOSIS OF HEPATITIS-C VIRUS (HCV) INFECTION USING AN IMMUNODOMINANT CHIMERIC POLYPROTEIN TO CAPTURE CIRCULATING ANTIBODIES - REEVALUATION OF THE ROLE OF HCV IN LIVER-DISEASE
DIAGNOSIS OF HEPATITIS-C VIRUS (HCV) INFECTION USING AN IMMUNODOMINANT CHIMERIC POLYPROTEIN TO CAPTURE CIRCULATING ANTIBODIES - REEVALUATION OF THE ROLE OF HCV IN LIVER-DISEASE
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DOI：
10.1073/pnas.89.21.10011
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
KUO, G
中科院分区：
文献类型：
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作者：
CHIEN, DY;CHOO, QL;KUO, G
hcv编码的多蛋白的结构和非结构区域已在重组酵母、细菌或昆虫细胞中表达，并用于捕获和测量不同个体循环的反应性抗体。推测的核衣壳蛋白(C)和非结构蛋白3-5 （NS3-NS5）含有最多的免疫显性表位。NS3、NS4和C区在酵母中以融合嵌合多蛋白（C25）的形式表达，并建立了反应性抗体的捕获方法。这种抗c25检测方法可以检测到所有先前确定的HCV血清阳性病例，并且对急性和慢性HCV感染的诊断比目前的抗c100 -3 （NS4）检测方法灵敏得多。在美国（95% vs. 71%）和日本（98% vs. 82%）、美国（62% vs. 28%）的隐源性肝硬化患者和日本（83% vs. 63%）的乙型肝炎表面抗原阴性肝细胞癌患者中，Anti-C25的检测频率高于抗c100 -3。这些数据表明，HCV在这些肝脏疾病中的作用比以前认为的要大。在引入抗c100 -3筛查后抽样的美国志愿献血者中，抗c25和抗c100 -3的患病率分别为0.5%和0.08%。
Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.