Pestka Jan M, Zeisel Mirjam B, Bläser Edith, Schürmann Peter, Bartosch Birke, Cosset Francois-Loïc, Patel Arvind H, Meisel Helga, Baumert Jens, Viazov Sergei, Rispeter Kay, Blum Hubert E, Roggendorf Michael, Baumert Thomas F
Department of Medicine II, University of Freiburg, 79106 Freiburg, Germany.
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6025-30. doi: 10.1073/pnas.0607026104. Epub 2007 Mar 28.
In contrast to a detailed understanding of antiviral cellular immune responses, the impact of neutralizing antibodies for the resolution of acute hepatitis C is poorly defined. The analysis of neutralizing responses has been hampered by the fact that patient cohorts as well as hepatitis C virus (HCV) strains are usually heterogeneous, and that clinical data from acute-phase and long-term follow-up after infection are not readily available. Using an infectious retroviral HCV pseudoparticle model system, we studied a cohort of women accidentally exposed to the same HCV strain of known sequence. In this single-source outbreak of hepatitis C, viral clearance was associated with a rapid induction of neutralizing antibodies in the early phase of infection. Neutralizing antibodies decreased or disappeared after recovery from HCV infection. In contrast, chronic HCV infection was characterized by absent or low-titer neutralizing antibodies in the early phase of infection and the persistence of infection despite the induction of cross-neutralizing antibodies in the late phase of infection. These data suggest that rapid induction of neutralizing antibodies during the early phase of infection may contribute to control of HCV infection. This finding may have important implications for understanding the pathogenesis of HCV infection and for the development of novel preventive and therapeutic antiviral strategies.
与对抗病毒细胞免疫反应的详细了解形成对比的是,中和抗体对急性丙型肝炎消退的影响尚不清楚。中和反应的分析受到以下因素的阻碍:患者队列以及丙型肝炎病毒(HCV)毒株通常具有异质性,并且感染后急性期和长期随访的临床数据不易获得。我们使用一种具有感染性的逆转录病毒HCV假颗粒模型系统,研究了一组意外接触相同已知序列HCV毒株的女性。在这次丙型肝炎的单源暴发中,病毒清除与感染早期中和抗体的快速诱导有关。从HCV感染恢复后,中和抗体减少或消失。相比之下,慢性HCV感染的特征是在感染早期中和抗体缺失或滴度较低,并且尽管在感染后期诱导了交叉中和抗体,但感染仍持续存在。这些数据表明,感染早期中和抗体的快速诱导可能有助于控制HCV感染。这一发现可能对理解HCV感染的发病机制以及开发新型预防性和治疗性抗病毒策略具有重要意义。