Determinants of viral clearance and persistence during acute hepatitis C virus infection.
Determinants of viral clearance and persistence during acute hepatitis C virus infection.
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DOI：
10.1084/jem.194.10.1395
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发表时间：
2001-11-19
期刊：
影响因子：
--
通讯作者：
Chisari FV
中科院分区：
文献类型：
--
作者：
Thimme R;Oldach D;Chang KM;Steiger C;Ray SC;Chisari FV
丙型肝炎病毒（HCV）感染的病毒学和免疫学特征进行了研究，每周为6个月后，意外针刺伤暴露在5名医护人员，其中4人发展为急性肝炎，进展为慢性，而一个主题清除病毒。在所有受试者中，在接种后1-2周内首次检测到病毒血症，在病毒特异性T细胞出现之前1个月或更长时间。清除病毒的受试者发生了急性肝炎的长期发作，与CD 38 + IFN-γ− CD 8 + T细胞对HCV的应答和病毒血症的小幅减少相一致。随后，出现了强烈的CD 4 + T细胞反应，CD 8 + T细胞变成CD 38 −，并开始产生IFN-γ以响应HCV，与病毒血症迅速减少100，000倍相一致，而没有相应的疾病活动激增。两名受试者未能产生显著的T细胞应答，另外两名受试者最初产生了强烈的CD 4 + T细胞应答，最终减弱。在所有受试者中，急性肝炎高峰期的病毒血症高于疾病开始时的病毒血症，并且在病毒血症期间疾病有所改善。这些结果提供了第一次深入了解宿主病毒的关系，在人类急性HCV感染的潜伏期，他们提供了唯一的洞察到目前为止的病毒学和免疫学特征的临床无症状的急性HCV感染，这种疾病的最常见的表现。此外，结果表明，抗病毒T细胞应答的活力和质量决定了急性HCV感染的结果，HCV超过T细胞应答的能力可能有助于其持续存在的趋势;肝炎的发作与CD 8 +T细胞反应的发作一致，疾病的发病机制和病毒清除是由不同的CD 8 + T细胞群介导的，这些T细胞群通过细胞溶解和非细胞溶解机制来控制HCV，在无症状和有症状的急性HCV感染中，病毒持续存在的途径不同。
The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1–2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-γ− CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38− and started producing IFN-γ in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host–virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.
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