title: Extracellular HCV-core protein induces an immature regulatory phenotype in NK cells: implications for outcome of acute infection.
abstract: BACKGROUND
  Hepatitis C viral (HCV) proteins, including core, demonstrate immuno-modulatory properties; however, the effect of extracellular core on natural killer (NK) cells has not previously been investigated.
  
  
  OBJECTIVE
  To characterise NKs in acute HCV infection over time, and, to examine the effect of exogenous HCV-core protein on NK cell phenotype and function.
  
  
  METHODS
  Acute HCV patients (n = 22), including 10 subjects who spontaneously recovered, were prospectively studied. Flow-cytometry was used to measure natural cytotoxicity and to phenotype NKs directly ex vivo and after culture with HCV-core protein. Microarray analysis was used to identify pathways involved in the NK cell response to exogenous HCV-core.
  
  
  RESULTS
  Direct ex vivo analysis demonstrated an increased frequency of immature/regulatory CD56bright NKs early in acute HCV infection per se which normalized with viral clearance. Natural cytotoxicity was reduced and did not recover after viral clearance. There was a statistically significant correlation between the frequency of CD56bright NKs and circulating serum levels of HCV core protein. In vitro culture of purified CD56bright NK cells with HCV-core protein in the presence of IL-15 maintained a significant proportion of NKs in the CD56bright state. The in vitro effect of core closely correlates with NK characteristics measured directly ex vivo in acute HCV infection. Pathway analysis suggests that HCV-core protein attenuates NK interferon type I responses.
  
  
  CONCLUSIONS
  Our data suggest that HCV-core protein alters NK cell maturation and may influence the outcome of acute infection.
authors: Division of Gastroenterology & Hepatology & Hepatitis C Center, University of Colorado, Aurora, Colorado, United States of America.
authors: Lucy
authors: L
authors: Golden-Mason
authors: Beirne Carter Center for Immunology Research, Department of Microbiology & Pathology, University of Virginia, Charlottesville, Virginia, United States of America.
authors: Young S
authors: YS
authors: Hahn
authors: Bioinformatics, Department of Medicine, University of Colorado, Aurora, Colorado, United States of America.
authors: Michael
authors: M
authors: Strong
authors: Division of Gastroenterology & Hepatology & Hepatitis C Center, University of Colorado, Aurora, Colorado, United States of America.
authors: Linling
authors: L
authors: Cheng
authors: Division of Gastroenterology & Hepatology & Hepatitis C Center, University of Colorado, Aurora, Colorado, United States of America; Denver Veterans Affairs (VA), Denver, Colorado, United States of America.
authors: Hugo R
authors: HR
authors: Rosen
mesh_terms: D000328:Adult; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D005110:Extracellular Space; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010641:Phenotype; D014758:Viral Core Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; D014758:Viral Core Proteins