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Int Immunopharmacol. 2015 Apr;25(2):545-52. doi: 10.1016/j.intimp.2015.02.037. Epub 2015 Mar 10.

Differential expression of interferon alpha inducible genes in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus and healthy donors.

Author information

1
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.
2
Novartis Oncology Companion Diagnostics, Cambridge, MA 02139, USA.
3
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.

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.

KEYWORDS:

Chronic hepatitis C virus infection; Interferon alpha therapy; Interferon alpha-induced gene expression; Peripheral blood mononuclear cells

PMID:
25765354
DOI:
10.1016/j.intimp.2015.02.037
[Indexed for MEDLINE]

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