title: Transcriptional Dysregulation of Upstream Signaling of IFN Pathway in Chronic HCV Type 4 Induced Liver Fibrosis.
abstract: IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention.
authors.affiliation: Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Marwa K
authors.initials: MK
authors.lastname: Ibrahim
authors.affiliation: Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Ghada Maher
authors.initials: GM
authors.lastname: Salum
authors.affiliation: Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Noha G
authors.initials: NG
authors.lastname: Bader El Din
authors.affiliation: Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Reham M
authors.initials: RM
authors.lastname: Dawood
authors.affiliation: Department of Microbiology, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Endemic Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khairy
authors.affiliation: Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: El Awady
mesh_terms: D000328:Adult; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000821:virology; D008103:Liver Cirrhosis / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D015398:Signal Transduction