A Conserved Domain of HCV E2 Glycoprotein Interacts with Human CD81 and Induces Interferon-Gamma Secretion from Peripheral Blood Mononuclear Cells

作者全名："Dai, Zhiyan; Zeng, Wei; Li, Gang; Shu, Xin"

作者地址："[Dai, Zhiyan] Chongqing Med Univ, Peoples Hosp Chengdu 3, Southwest Jiaotong Univ, Affiliated Hosp,Dept Gastroenterol & Hepatol, Chengdu 610031, Sichuan, Peoples R China; [Zeng, Wei] Chongqing Med Univ, Peoples Hosp Chengdu 3, Southwest Jiaotong Univ, Affiliated Hosp,Dept Crit Care Med, Chengdu 610031, Sichuan, Peoples R China; [Li, Gang; Shu, Xin] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Infect Dis, Guangzhou 510630, Guangdong, Peoples R China"

通信作者："Dai, ZY (通讯作者)，Chongqing Med Univ, Peoples Hosp Chengdu 3, Southwest Jiaotong Univ, Affiliated Hosp,Dept Gastroenterol & Hepatol, Chengdu 610031, Sichuan, Peoples R China."

来源：FRONTIERS IN BIOSCIENCE-LANDMARK

ESI学科分类：　

WOS号：WOS:001106813700007

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：28

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：hepatitis C virus; E2 glycoprotein; conserved domain; hCD81; protein-protein interaction; interferon-gamma; immune response

摘要："Background: Hepatitis C virus (HCV) infection is a global health threat to the public, and vaccines against it are not yet available. The HCV envelope glycoprotein E2 is a key target for anti-HCV vaccines. The majority of previous studies have focused on the hypervariable region and the glycosylation sites of the_HCV structural protein. This study aims to investigate a conserved domain of HCV E2 glycoprotein and explore its potential to induce an immune response against HCV. Methods: HCV E2 conserved domain (encompassing amino acids 505-702) was prepared in Escherichia coli (E. coli). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HCV or healthy controls. Interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assay was conducted to examine the HCV E2-specific immune response as reflected by IFN-gamma-secreting cells/10(6) PBMCs. Results: HCV E2 conserved domain was highly conserved among 25 HCV subtypes, and its recombinant soluble production in E. coli was recognized by anti-HCV E2 monoclonal antibodies. This study characterized in vitro direct interaction between bacterially expressed HCV E2 conserved domain and human CD81 (hCD81). Furthermore, the recombinant HCV E2_conserved domain markedly induced the production of IFN-gamma by PBMCs from patients with HCV. Its stimulated specific immune response was significantly different from non-specific peptide controls or PBMCs isolated from healthy controls. Conclusions: HCV E2 conserved domain directly binds hCD81 and activates the production of IFN-gamma in the PBMCs of patients with HCV. Therefore, the conserved domain of HCV E2 glycoprotein may be a new candidate for developing an HCV vaccine."

基金机构：Research Unit and Vaccine Research Institute of the Third Affiliated Hospital of Sun Yat-sen University; Gene Therapy Program of the University of Pennsylvania

基金资助正文："This work was supported by the Research Unit and Vaccine Research Institute of the Third Affiliated Hospital of Sun Yat-sen University, and Gene Therapy Program of the University of Pennsylvania."