title: Hepatitis C virus protects human B lymphocytes from Fas-mediated apoptosis via E2-CD81 engagement.
abstract: HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ren
authors.forename: Yimin
authors.initials: Y
authors.lastname: Tong
authors.forename: Xian
authors.initials: X
authors.lastname: Hua
authors.forename: Fenghui
authors.initials: F
authors.lastname: Zhu
authors.forename: Libin
authors.initials: L
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Zhongtian
authors.initials: Z
authors.lastname: Qi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D019610:Cytoprotection; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008213:Lymphocyte Activation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D000091402:Prohibitins; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D060225:Tetraspanin 28; D015854:Up-Regulation; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C554798:CD81 protein, human; C491901:FAS protein, human; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000717328:PHB protein, human; D000091402:Prohibitins; D019253:Proto-Oncogene Proteins c-bcl-2; D011991:Receptors, Virus; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; D019014:fas Receptor; D000072000:NF-KappaB Inhibitor alpha; C091015:glycoprotein E2, Hepatitis C virus