Hepatitis C virus (HCV) core protein genotype 3a induces the expression of suppressor of cytokine signalling protein 7 (SOCS-7), which is partially involved in the development of insulin resistance. The aim of the present study was to investigate the mechanism through which the core protein regulates SOCS-7 expression. We have explored, in the in vitro model of Huh-7 cells expressing the HCV core protein of genotype 3a, whether the expression of SOCS-7 as well as of other members of the SOCS family (SOCS-1 and SOCS-3) was activated by the STAT3 pathway, using immunoblotting and real-time PCR upon alpha interferon (IFN-α) treatment. We found that, whilst IFN-α treatment induced STAT3 activation and consequently SOCS-1 and SOCS-3 upregulation in HCV genotype 3a core-expressing Huh-7 cells, SOCS-7 mRNA expression was independent of STAT3 and seemed to be modulated by peroxisome proliferator-activated receptor gamma (PPAR-γ) activity, as demonstrated by quantitative real-time PCR and immunoblot detection after treatment with the PPAR-γ agonist rosiglitazone or the PPAR-γ antagonist GW9262. In contrast to the other studied members of the SOCS family (1 and 3), which are regulated by STAT3 activation, SOCS-7 expression appears to be STAT3-independent and seems to be regulated instead by PPAR-γ. This is the first report proposing a molecular mechanism through which the HCV core protein (genotype 3a) modulates SOCS-7 expression.
ASJC Scopus subject areas