title: Decreased interferon-alpha production and impaired regulatory function of plasmacytoid dendritic cells induced by the hepatitis C virus NS 5 protein.
abstract: pDC are known to produce large amount of IFN-alpha/beta in response to viruses, and act as a major link between the innate and adaptive immune response. This study concentrated on the interaction of human peripheral blood derived pDC with HCV NS3, NS4, and NS5 proteins, and their maturation, cytokine secretion and functional properties. It was shown that HCV NS5 interferes with CD40L induced maturation of pDC as indicated by decreased expression of CD83 and CD86 markers. CpG ODN stimulated HCV NS3 and NS5 treated pDC showed decreased production of IFN-alpha. In the case of NS3, IFN-alpha production was reduced to 126 pg/ml as compared to 245 pg/ml in controls (P < 0.01), and with NS5, IFN-alpha production was reduced to 92 pg/ml as compared to 238 pg/ml in controls (P < 0.05). In the presence of HCV NS5, the T cell stimulatory capacity of pDC was impaired, as indicated by decreased proliferation of T cells, and decreased production by the T cells of IFN-gamma, which were down to 86 pg/ml as compared to 260 pg/ml in controls (P < 0.05). These results suggest that HCV NS5 impairs pDC function and is in agreement with several other in vivo studies indicating decreased numbers of, and dysfunctional pDC, in chronic HCV infected patients.
authors.affiliation: Clinical Laboratory Science Program, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, USA. m.amjad@wayne.edu
authors.forename: Muhammad
authors.initials: M
authors.lastname: Amjad
authors.forename: Nahed
authors.initials: N
authors.lastname: Abdel-Haq
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faisal
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kamal
authors.forename: Varsha
authors.initials: V
authors.lastname: Moudgal
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D000097802:CD83 Antigen; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D007136:Immunoglobulins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012313:RNA; D017361:Viral Nonstructural Proteins; D000097802:CD83 Antigen; C408982:CPG-oligonucleotide; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase