Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection

作者：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^*

来源：iScience, 2023, 26(4): 106421.

DOI：10.1016/j.isci.2023.106421

• HUMAN MONOCLONAL-ANTIBODIES
• T-CELL RESPONSES
• B TYPE-I
• NEUTRALIZING ANTIBODIES
• HYPERIMMUNE SERUM
• MUTATIONS
• EVOLUTION
• PROTEINS
• VACCINE
• GLYCOPROTEIN

Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during nat-ural 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 an-tibodies 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 re-ceptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established in-fections of multiple HCV genotypes.

• 单位
  5; 中山大学; 广州医学院; 南方医科大学