Deng Kai, Zhou Qing, Xu Zhanxue, Yang Yuhao, Liu Xi, Li Chunna, Chen Mingxiao, Zhang Zhenzhen, Chen Haihang, Ma Ling, Anwar Muhammad Ikram, Zheng Changlong, Rong Liang, Huang Mingxing, Xia Jinyu, Zhou Yuanping, Li Yi-Ping
Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
iScience. 2023 Mar 16;26(4):106421. doi: 10.1016/j.isci.2023.106421. eCollection 2023 Apr 21.
Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.
在自然丙型肝炎病毒（HCV）感染过程中产生的靶向高变区1（HVR1）的抗体是否有助于病毒清除以及其潜在机制尚不清楚。在此，我们证明，用从28例慢性丙型肝炎（CHC）患者中的2例（7.1%）纯化的IgG处理HCV感染的肝癌Huh7.5细胞，可有效控制感染，其中基因型1b HVR1（1bHVR1）结合抗体至关重要。此外，我们发现1bHVR1肽在兔免疫中比2aHVR1更能有效诱导中和基因型1a、2a、3a和4a的抗体。1bHVR1 IgG的中和作用可被HH-1增强，HH-1是一种由CHC记忆B细胞构建但不与HVR1肽结合的抗体。机制研究表明，1bHVR1抗血清和IgG破坏了E2-SR-B1受体的相互作用。本研究强调了CHC患者产生的以及通过HVR1免疫产生的HVR1抗体对多种HCV基因型已建立感染的中和活性。
