Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Host Microbe. 2018 Nov 14;24(5):717-730.e5. doi: 10.1016/j.chom.2018.10.012.
The role that broadly neutralizing antibodies (bNAbs) play in natural clearance of human hepatitis C virus (HCV) infection and the underlying mechanisms remain unknown. Here, we investigate the mechanism by which bNAbs, isolated from two humans who spontaneously cleared HCV infection, contribute to HCV control. Using viral gene sequences amplified from longitudinal plasma of the two subjects, we found that these bNAbs, which target the front layer of the HCV envelope protein E2, neutralized most autologous HCV strains. Acquisition of resistance to bNAbs by some autologous strains was accompanied by progressive loss of E2 protein function, and temporally associated with HCV clearance. These data demonstrate that bNAbs can mediate clearance of human HCV infection by neutralizing infecting strains and driving escaped viruses to an unfit state. These immunopathologic events distinguish HCV from HIV-1 and suggest that development of an HCV vaccine may be achievable.
广谱中和抗体（bNAbs）在人体自然清除丙型肝炎病毒（HCV）感染中的作用及其潜在机制尚不清楚。在这里，我们研究了从两名自然清除 HCV 感染的个体中分离出来的 bNAbs 对 HCV 控制的作用机制。我们利用从两名受试者的纵向血浆中扩增的病毒基因序列发现，这些靶向 HCV 包膜蛋白 E2 前层的 bNAbs 可以中和大多数同源 HCV 株。一些同源株对 bNAbs 的耐药性获得伴随着 E2 蛋白功能的逐渐丧失，并与 HCV 的清除时间相关。这些数据表明，bNAbs 通过中和感染株并将逃逸的病毒推向不适宜状态，可以介导人体 HCV 感染的清除。这些免疫病理事件将 HCV 与 HIV-1 区分开来，并表明 HCV 疫苗的开发可能是可行的。
