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Title

The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms

Authors
Mangia, Alessandra
Published in Hepatology. 2007, vol. 45, no. 5, p. 1164-71
Abstract Both molecular and clinical evidence support a link between HCV infection and insulin resistance. We examined the in vitro interaction between the HCV core protein of genotypes 3a and 1b with the insulin-signaling pathway. We measured the expression levels of insulin receptor substrate 1 (IRS-1), IRS-2, and other factors involved in the insulin signal pathway in a human hepatoma cell line (Huh-7) transiently expressing the HCV core protein of genotypes 3a or 1b by molecular biology and biochemical techniques. The IRS-1 (but not IRS-2) protein level was significantly reduced in Huh-7 expressing the core protein of both genotypes 3a and 1b, as compared to cells transfected with the empty vector. However, while the core protein of genotype 3a promoted IRS-1 degradation through the downregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) and by upregulating the suppressor of cytokine signal 7 (SOCS-7), the core protein of genotype 1b activated the mammalian target of rapamycin (mTOR). We confirmed these findings by using agonists for PPARgamma (rosiglitazone) or short interfering RNAs for SOCS-7.
Keywords Amino Acid SequenceCarcinomaHepatocellularCell LineTumorDown-RegulationHepacivirus/geneticsHumansInsulin Receptor Substrate ProteinsLiver NeoplasmsNuclear Proteins/physiologyPPAR gamma/physiologyPhosphoproteins/biosynthesisProteasome Endopeptidase Complex/metabolismSerine/metabolismSuppressor of Cytokine Signaling Proteins/physiologyTransfectionViral Core Proteins/genetics/physiology
Identifiers
PMID: 17465001
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Research group Obésité et syndrome métabolique (803)
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PAZIENZA, Valerio et al. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. In: Hepatology, 2007, vol. 45, n° 5, p. 1164-71. https://archive-ouverte.unige.ch/unige:90665

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Deposited on : 2016-12-21

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