title: Hepatitis C virus infection in vitro triggers endoplasmic reticulum stress and downregulates insulin receptor substrates 1 and 2 through upregulation of cytokine signaling suppressor 3.
abstract: Hepatitis C virus (HCV) infection is highly prevalent worldwide and most of HCV infections enter into chronic phase subsequently leading to insulin resistance (IR) and clinical complications. Although the clinics of chronic HCV infection is well described, there is need to better understand the molecular mechanisms of HCV-induced IR. Therefore this study was aimed to unveil the role of host genes involved in the development of HCV-induced IR. For this purpose the expression of selected genes in HCV-infected and non-infected Huh-7 cells at various time post infection (p.i.) was assayed by real-time PCR. HCV infection was found to trigger endoplasmic reticulum (ER) stress response as demonstrated by an increase in the expression of calreticulin (Cal) gene but no change in the expression of Gadd153 gene. The infection also enhanced the expression of suppressor of cytokine signaling 3 (SOCS-3), responsible for the degradation of insulin receptor substrates (IRS). Moreover, it led to a decreased expression of key signaling molecules IRS-1 and IRS-2, unchanged expression of SOCS-7 and increased expression of downstream signaling molecule Akt. Altogether these findings indicate that the HCV infection induces ER stress and IR in Huh-7 cells in vitro.
authors.forename: Q L
authors.initials: QL
authors.lastname: Ahmed
authors.forename: S
authors.initials: S
authors.lastname: Manzoor
authors.forename: M
authors.initials: M
authors.lastname: Tariq
authors.forename: M
authors.initials: M
authors.lastname: Khalid
authors.forename: W
authors.initials: W
authors.lastname: Ashraf
authors.forename: F
authors.initials: F
authors.lastname: Parvaiz
authors.forename: M
authors.initials: M
authors.lastname: Imran
mesh_terms: D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D055504:Insulin Receptor Substrate Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins