Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection
Summary: 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 pu...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223004984 |
| _version_ | 1797856425631809536 |
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| author | Kai Deng Qing Zhou Zhanxue Xu Yuhao Yang Xi Liu Chunna Li Mingxiao Chen Zhenzhen Zhang Haihang Chen Ling Ma Muhammad Ikram Anwar Changlong Zheng Liang Rong Mingxing Huang Jinyu Xia Yuanping Zhou Yi-Ping Li |
| author_facet | Kai Deng Qing Zhou Zhanxue Xu Yuhao Yang Xi Liu Chunna Li Mingxiao Chen Zhenzhen Zhang Haihang Chen Ling Ma Muhammad Ikram Anwar Changlong Zheng Liang Rong Mingxing Huang Jinyu Xia Yuanping Zhou Yi-Ping Li |
| author_sort | Kai Deng |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T20:40:14Z |
| format | Article |
| id | doaj.art-8bfcc8f21cda40ea9d9e0294d0c755b8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T20:40:14Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8bfcc8f21cda40ea9d9e0294d0c755b82023-03-30T04:26:56ZengElsevieriScience2589-00422023-04-01264106421Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infectionKai Deng0Qing Zhou1Zhanxue Xu2Yuhao Yang3Xi Liu4Chunna Li5Mingxiao Chen6Zhenzhen Zhang7Haihang Chen8Ling Ma9Muhammad Ikram Anwar10Changlong Zheng11Liang Rong12Mingxing Huang13Jinyu Xia14Yuanping Zhou15Yi-Ping Li16Institute 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, ChinaInstitute 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; Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, ChinaInstitute 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, ChinaInstitute 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, ChinaDepartment of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, ChinaDepartment of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaInstitute 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, ChinaDepartment of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, ChinaInstitute 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, ChinaDepartment of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, ChinaDepartment of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, ChinaGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaInstitute 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; Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223004984ImmunologyVirology |
| spellingShingle | Kai Deng Qing Zhou Zhanxue Xu Yuhao Yang Xi Liu Chunna Li Mingxiao Chen Zhenzhen Zhang Haihang Chen Ling Ma Muhammad Ikram Anwar Changlong Zheng Liang Rong Mingxing Huang Jinyu Xia Yuanping Zhou Yi-Ping Li Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection iScience Immunology Virology |
| title | Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection |
| title_full | Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection |
| title_fullStr | Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection |
| title_full_unstemmed | Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection |
| title_short | Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection |
| title_sort | hepatitis c virus hypervariable region 1 antibodies interrupt e2 sr b1 interaction to suppress viral infection |
| topic | Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223004984 |
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