title: Differential expression of interferon alpha inducible genes in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus and healthy donors.
abstract: The impact of exposure to interferon-alpha (IFN-α) on gene expression in peripheral blood mononuclear cells (PBMC) from hepatitis C virus (HCV)-infected and healthy individuals was investigated to recognize whether their PBMC differ in expression of IFN-inducible genes (ISGs) following treatment with IFN-α2b. PBMC obtained from healthy and treatment-naïve HCV-infected patients were cultured with IFN-α2b for 30min, 2h, 4h and 72h, and gene expression was analyzed using mRNA microarray technology. IFN-α caused differential up-regulation of many known ISGs in PBMC from both HCV-infected and healthy subjects. In comparison to untreated controls, the highest augmentation in PBMC ISG expression occurred after 4-hour exposure to IFN-α2b in both groups. The analysis identified 84 transcripts, representing 64 known and 2 unknown genes, that were up-regulated by at least 5-fold in PBMC from infected and uninfected individuals. However, the expression of IFN-α inducible genes was impaired in the PBMC from HCV-infected individuals compared to healthy controls. This was due to an increased baseline expression of the transcripts in PBMC of HCV-infected patients. These findings expand our understanding of IFN-responses in HCV-infected individuals and suggest that functions of PBMC, which include immune effector cells, are altered in patients chronically infected with HCV.
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 A1B 3V6, Canada.
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 A1B 3V6, Canada.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Corkum
authors.affiliation: Novartis Oncology Companion Diagnostics, Cambridge, MA 02139, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Burgess
authors.affiliation: Novartis Oncology Companion Diagnostics, Cambridge, MA 02139, USA.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Karwowska
authors.affiliation: Novartis Oncology Companion Diagnostics, Cambridge, MA 02139, USA.
authors.forename: Werner
authors.initials: W
authors.lastname: Kroll
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 A1B 3V6, Canada. Electronic address: timich@mun.ca.
authors.forename: Tomasz I
authors.initials: TI
authors.lastname: Michalak
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins
keywords: Chronic hepatitis C virus infection; Interferon alpha therapy; Interferon alpha-induced gene expression; Peripheral blood mononuclear cells