title: Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-αR expression regulates signaling and is implicated in IFN-α-induced hepatitis C virus decline.
abstract: BACKGROUND
  Natural killer (NK) cells likely contribute to outcome of acute hepatitis C virus (HCV) infection and interferon (IFN)-induced control of chronic HCV infection. We previously observed IFN-αR and NKp30 expression associated with IFN-α-dependent NK cell activity.
  
  
  METHODS
  Here, we examined CD16(+)56(-), CD16(+)56(+), and CD16(-)56(+) NK cell subset IFN-αR and NKp30 expression in relation to magnitude of HCV genotype 1 decrease during pegylated IFN-α plus ribavirin therapy.
  
  
  RESULTS
  We observed greater baseline IFN-αR and NKp30 expression on CD16(+)56(+) and CD16(-)56(+) NK subsets in HCV-infected patients than in healthy control subjects. Baseline CD16(+)56(-) NK IFN-αR expression was associated with IFN-α-induced pSTAT1, and both were associated with magnitude of HCV decrease during pegylated IFN-α plus ribavirin therapy. Baseline CD16(+)56(-) NK IFN-αR expression was associated with race and interleukin 28B genotype, negatively associated with aspartate aminotransferase-to platelet ratio index, and positively associated with increase in NKp30 expression after in vivo IFN-α exposure. Finally, in vitro IFN-α2a-activated NK cytolysis of HCV-infected target cells was in part dependent on NKp30, and CD16(+)56(-) NK cell IFN-αR expression correlated with cytolytic activity.
  
  
  CONCLUSIONS
  IFN-αR expression on CD16(+)56(-) NK cells during chronic HCV infection may in part be genetically determined, and level of expression regulates IFN-α signaling, which in turn may contribute to control of HCV infection.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Conry
authors.forename: Qinglai
authors.initials: Q
authors.lastname: Meng
authors.forename: Gareth
authors.initials: G
authors.lastname: Hardy
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yonkers
authors.forename: Julia M
authors.initials: JM
authors.lastname: Sugalski
authors.forename: Amy
authors.initials: A
authors.lastname: Hirsch
authors.forename: Perica
authors.initials: P
authors.lastname: Davitkov
authors.forename: Anita
authors.initials: A
authors.lastname: Compan
authors.forename: Yngve
authors.initials: Y
authors.lastname: Falck-Ytter
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Blanton
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: Donald D
authors.initials: DD
authors.lastname: Anthony
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D019002:CD56 Antigen / Q000032:analysis; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000096:biosynthesis / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis* / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; C522918:NCAM1 protein, human; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D053633:Receptor, Interferon alpha-beta