title: Patient-derived hepatitis C virus inhibits CD4⁺ but not CD8⁺ T lymphocyte proliferation in primary T cells.
abstract: BACKGROUND
  Hepatitis C virus (HCV) can replicate in cells of the immune system and productively propagate in primary T lymphocytes in vitro. We aimed to determine whether exposure to authentic, patient-derived HCV can modify the proliferation capacity, susceptibility to apoptosis and phenotype of T cells.
  
  
  METHODS
  Primary total T cells from a healthy donor were used as targets and plasma-derived HCV from patients with chronic hepatitis C served as inocula. T cell phenotype was determined prior to and at different time points after exposure to HCV. T cell proliferation and apoptosis were measured by flow cytometry-based assays.
  
  
  RESULTS
  The HCV inocula that induced the highest intracellular expression of HCV also caused a greatest shift in the T cell phenotype from predominantly CD4-positive to CD8-positive. This shift was associated with inhibition of CD4+ but not CD8+ T cell proliferation and did not coincide with altered apoptotic death of either cell subset.
  
  
  CONCLUSIONS
  The data obtained imply that exposure to native HCV can have an impact on the relative frequencies of CD4+ and CD8+ T cells by selectively suppressing CD4(+) T lymphocyte proliferation and this may occur in both the presence and the absence of measurable HCV replication in these cells. If the virus exerts a similar effect in vivo, it may contribute to the impairment of virus-specific T cell response by altering cooperation between immune cell subsets.
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland and Labrador, Canada. sonyamacparland@gmail.com.|Present address: Department of Immunology, Medical Sciences Building, University of Toronto, Toronto, ON, Canada. sonyamacparland@gmail.com.
authors.forename: Sonya A
authors.initials: SA
authors.lastname: MacParland
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland and Labrador, Canada. chenyan03@hotmail.com.
authors.forename: Annie Y
authors.initials: AY
authors.lastname: Chen
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland and Labrador, Canada. c.corkum@mun.ca.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Corkum
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland and Labrador, Canada. Tram.Pham@ircm.qc.ca.|Present address: Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC, Canada. Tram.Pham@ircm.qc.ca.
authors.forename: Tram N Q
authors.initials: TN
authors.lastname: Pham
authors.affiliation: Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University, St. John's, Newfoundland and Labrador, Canada. timich@mun.ca.
authors.forename: Tomasz I
authors.initials: TI
authors.lastname: Michalak
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D019562:Viral Load
chemical_list: D000954:Antigens, Surface; D000998:Antiviral Agents; D016207:Cytokines; D009842:Oligopeptides; C486464:telaprevir