Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Key Laboratory of Medical Molecular Virology (MOE/MOH), Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Viruses. 2022 Sep 11;14(9):2011. doi: 10.3390/v14092011.
Anti-HBc IgG is usually recognized as a diagnostic marker of hepatitis B, while the functional role anti-HBc IgG in HBV infection has not been fully elucidated. In this study, we firstly investigated the relationship between the anti-HBc IgG responses and the replication of HBV using AAV8-1.3HBV infected C57BL/6N mice. Our data showed that the anti-HBc IgG responses at the early phase of infection correlated negatively with the concentrations of circulating HBsAg and HBV DNA at both the early and chronic phases of infection. This observation was confirmed by an independent experiment using AAV8-1.3HBV infected C57BL/6J mice. Furthermore, to comprehend the potential causal relationship between the anti-HBc IgG responses and HBV infection, mice were treated with an anti-HBc monoclonal antibody at three days post AAV8-1.3HBV infection. Our data showed that the anti-HBc mAb significantly suppressed the fold increase of circulating HBsAg level, and the protective effect was not affected by NK cell depletion. Collectively, our study demonstrated that anti-HBc antibodies occurring at the early phase of HBV infection may contribute to the constraint of the virus replication, which might be developed as an immunotherapy for hepatitis B.
抗-HBc IgG 通常被认为是乙型肝炎的诊断标志物,而抗-HBc IgG 在乙型肝炎病毒感染中的功能作用尚未完全阐明。在这项研究中,我们首次使用 AAV8-1.3HBV 感染的 C57BL/6N 小鼠研究了抗-HBc IgG 反应与乙型肝炎病毒复制之间的关系。我们的数据显示,感染早期的抗-HBc IgG 反应与感染早期和慢性阶段的循环 HBsAg 和 HBV DNA 浓度呈负相关。这一观察结果通过使用 AAV8-1.3HBV 感染的 C57BL/6J 小鼠进行的独立实验得到了证实。此外,为了理解抗-HBc IgG 反应与乙型肝炎病毒感染之间的潜在因果关系,我们在 AAV8-1.3HBV 感染后三天用抗-HBc 单克隆抗体处理小鼠。我们的数据显示,抗-HBc mAb 显著抑制了循环 HBsAg 水平的倍增,并且这种保护作用不受 NK 细胞耗竭的影响。总之,我们的研究表明,乙型肝炎病毒感染早期出现的抗-HBc 抗体可能有助于限制病毒复制,这可能被开发为乙型肝炎的免疫疗法。