title: Interferon alfa down-regulates CD81 in patients with chronic hepatitis C.
abstract: CD81 protein has been shown to bind hepatitis C virus (HCV) envelope 2 (E2) glycoprotein in vitro and may act as a (co)receptor for HCV. Regulation of CD81 expression by interferon alfa (IFN-alpha) and ribavirin could thereby affect the response to antiviral therapy. In the present study, the effects of IFN-alpha and ribavirin on CD81 protein and CD81 mRNA were assessed in peripheral blood lymphocytes (PBL) and isolated human hepatocytes by fluorescence-activated cell sorter (FACS) analysis and real-time polymerase chain reaction (PCR), respectively. In addition, regulation of CD81 in PBL was investigated in 10 patients treated with combination therapy. Incubation with IFN-alpha (50 U/mL) down-regulated total CD81 in PBL (81.7 +/- 11.6% of control; P =.003) and in isolated human hepatocytes (91.6 +/- 8.1% of control; P =.034). Incubation with IFN-alpha with and without ribavirin (2.2 microg/mL) significantly reduced cell surface-associated CD81 protein (83.9 +/- 10.3% of control; P =.003). PBL of untreated patients chronically infected with HCV had significantly higher levels of total CD81 protein compared with PBL obtained from healthy donors (631.1 +/- 93.3 vs. 538.9 +/- 95.2 relative fluorescence units [RFU]; P =.030). Pretreatment cell surface-associated CD81 protein was lower in patients infected with genotype HCV-3 than those infected with HCV-1 (111.8 +/- 15.0 vs. 162.0 +/- 41.3 RFU; P =.019). Furthermore, cell surface-associated CD81 protein was lower 4 weeks after initiation of therapy in patients with an initial virologic response compared with initial virologic nonresponders (110.5 +/- 8.5 vs. 139.8 +/- 27.5 RFU; P =.057). In conclusion, IFN-alpha and ribavirin regulate CD81 expression in vitro and in vivo. CD81 expression correlates with HCV genotype and initial virologic response in patients with chronic hepatitis C.
authors.affiliation: Medizinische Klinik II, Klinik für Allgemein- und Abdominalchirurgie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kronenberger
authors.forename: B
authors.initials: B
authors.lastname: Rüster
authors.forename: R
authors.initials: R
authors.lastname: Elez
authors.forename: S
authors.initials: S
authors.lastname: Weber
authors.forename: A
authors.initials: A
authors.lastname: Piiper
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: W K
authors.initials: WK
authors.lastname: Roth
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004338:Drug Combinations; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D004338:Drug Combinations; D016898:Interferon-alpha; D008565:Membrane Proteins; D012333:RNA, Messenger; D060225:Tetraspanin 28; D012254:Ribavirin