title: Activation of natural killer cells by hepatitis C virus particles in vitro.
abstract: Little is known about the ability of hepatitis C virus (HCV) to alter early innate immune responses in infected patients. Previous studies have shown that natural killer (NK) cells are functionally impaired after interaction of recombinant HCV glycoprotein E2 with the co-stimulatory CD81 molecule in vitro; however, the functional consequences of a prolonged contact of NK cells with HCV particles have remained unclear. We have examined the phenotypes of purified, interleukin-2-activated NK cells from healthy donors and HCV genotype 1b patients after culture for 5 days with HCV pseudoparticles (HCVpp) and serum samples containing HCV genotype 1b. NK cells from healthy donors and chronic HCV patients were found to up-regulate receptors associated with activation (NKp46, NKp44, NKp30, NKG2D), while NK receptors from the killer cell immunoglobulin-like receptor family (KIR/CD158), predominantly having an inhibitory function, were significantly down-modulated after culture in the presence of HCV particles compared with control cultures of NK cells. HCV-infected sera and HCVpp elicited significantly higher secretion of the NK effector lymphokines interferon-γ and tumour necrosis factor-α. Furthermore, HCV stimulated the cytotoxic potential of NK cells from normal donors and patients. The enhanced activation of NK cells after prolonged culture with HCVpp or HCV-containing sera for 5 days suggests that these innate effector cells may play an important role in viral control during early phases of HCV infection.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Clinic IV, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: M M S
authors.initials: MM
authors.lastname: Farag
authors.forename: K
authors.initials: K
authors.lastname: Weigand
authors.forename: J
authors.initials: J
authors.lastname: Encke
authors.forename: F
authors.initials: F
authors.lastname: Momburg
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D058851:GPI-Linked Proteins / Q000378:metabolism; D057809:HEK293 Cells; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D037102:Lectins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D054340:Receptors, KIR / Q000378:metabolism; D060225:Tetraspanin 28; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014758:Viral Core Proteins / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics; D014771:Virion / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; C554798:CD81 protein, human; D017077:Culture Media, Conditioned; C087035:E1 protein, Hepatitis C virus; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C497869:KLRD1 protein, human; C527085:KLRK1 protein, human; D037102:Lectins; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D054340:Receptors, KIR; C402206:SIGLEC7 protein, human; D060225:Tetraspanin 28; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D007371:Interferon-gamma