2. Academic Validation
  3. Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection

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

  • iScience. 2023 Mar 16;26(4):106421. doi: 10.1016/j.isci.2023.106421.
Kai Deng 1 2,  Qing Zhou 1 3,  Zhanxue Xu 1,  Yuhao Yang 1,  Xi Liu 4,  Chunna Li 4,  Mingxiao Chen 1,  Zhenzhen Zhang 1,  Haihang Chen 1,  Ling Ma 1,  Muhammad Ikram Anwar 1,  Changlong Zheng 5,  Liang Rong 1,  Mingxing Huang 4,  Jinyu Xia 4,  Yuanping Zhou 6,  Yi-Ping Li 1 3 4
Affiliations

Affiliations

  • 1 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.
  • 2 Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • 3 Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 4 Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
  • 5 Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 6 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
PMID: 37034976 DOI: 10.1016/j.isci.2023.106421
Abstract

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.

Keywords

Immunology; Virology.

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