Humoral immune response in acute hepatitis C virus infection
Humoral immune response in acute hepatitis C virus infection
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DOI：
10.1086/432478
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发表时间：
2005-09-01
影响因子：
11.8
通讯作者：
Cox, A
中科院分区：
文献类型：
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作者：
Netski, DM;Mosbruger, T;Cox, A
背景。关于急性丙型肝炎病毒（HCV）感染的抗体反应的时间、强度、特异性和临床相关性的信息很少。通过对12名注射吸毒者在感染前、感染中和感染后的抗体反应，研究了抗体的特异性、滴度和中和电位。血清转化被定义为使用市售酶联免疫吸附试验（ELISA）检测hcv特异性抗体的事件。HCV蛋白特异性抗体反应采用ELISA法检测重组抗原。为了进行中和试验，血浆与人类免疫缺陷病毒(HIV)-HCV H77或对照HIV-小鼠白血病病毒（MLV）假型病毒孵育，然后让其感染Hep3B肝癌细胞。到HCV血清转化的平均时间为病毒血症发生后6周。在对结构蛋白产生应答之前检测到对非结构蛋白的抗体应答，并且对这两种蛋白的抗体主要局限于免疫球蛋白G1 （IgG1）亚类。对结构蛋白和非结构蛋白的抗体应答的最大中位终点滴度分别为1:6 00和1:6 400。仅1名受试者在血清转化时检测到中和携带HCV 1a包膜糖蛋白的逆转录病毒伪型的抗体，3名受试者在血清转化后6-8个月检测到抗体。中和抗体的延迟出现与病毒包膜糖蛋白特异性抗体的晚发育一致，这些抗体被认为介导了病毒中和。急性HCV感染的体液免疫反应滴度相对较低，主要局限于IgG1亚类，并且是延迟的。更好地了解中和抗体产生延迟的原因可能有助于预防丙型肝炎病毒感染。
Background. There is little information on the timing, magnitude, specificity, and clinical relevance of the antibody response to acute hepatitis C virus (HCV) infection. We investigated the specificity, titer, and neutralizing potential of antibody responses to acute infection by examining 12 injection drug users before, during, and after infection.Methods. Seroconversion was defined as incident detection of HCV-specific antibodies by using a commercially available enzyme-linked immuosorbent assay (ELISA). HCV protein-specific antibody responses were measured using recombinant antigens in an ELISA. For neutralization assays, plasma was incubated with human immunodeficiency virus (HIV)-HCV H77 or control HIV-murine leukemia virus (MLV) pseudotype virus and then allowed to infect Hep3B hepatoma cells.Results. The mean time to HCV seroconversion was 6 weeks after the onset of viremia. Antibody responses to nonstructural proteins were detected before responses to the structural proteins, and antibodies to both were primarily restricted to the immunoglobulin G1 (IgG1) subclass. The maximum median end point titers for antibody responses to structural and nonstructural proteins were 1: 600 and 1: 6400, respectively. Antibodies that neutralized a retroviral pseudotype bearing HCV 1a envelope glycoproteins were detected at seroconversion in only 1 subject and at 6-8 months after seroconversion in 3 subjects. The delayed appearance of neutralizing antibodies was consistent with the late development of antibodies specific for the viral envelope glycoproteins, which are believed to mediate virus neutralization.Conclusion. The humoral immune response to acute HCV infection is of relatively low titer, is restricted primarily to the IgG1 subclass, and is delayed. A better understanding of why production of neutralizing antibody is delayed may improve efforts to prevent HCV infection.