title: Differential regulation of SOCS-1 signalling in B and T lymphocytes by hepatitis C virus core protein.
abstract: Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core-gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-gamma production in CD8+ T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20+ B cells. Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription-polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.
authors.affiliation: Medical Service, James H. Quillen VAMC, and Department of Internal Medicine, Division of Infectious Diseases, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Yao
authors.forename: Deborah
authors.initials: D
authors.lastname: Prayther
authors.forename: Christopher
authors.initials: C
authors.lastname: Trabue
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Dong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moorman
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D024101:Mitochondrial Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D018936:Hepatitis C Antigens; D024101:Mitochondrial Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus