Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis
Article first published online: 18 APR 2011
Copyright © 2011 Wiley-Liss, Inc.
Journal of Medical Virology
Volume 83, Issue 6, pages 1005–1015, June 2011
How to Cite
Pascarella, S., Clément, S., Guilloux, K., Conzelmann, S., Penin, F. and Negro, F. (2011), Effects of hepatitis C virus on suppressor of cytokine signaling mRNA levels: Comparison between different genotypes and core protein sequence analysis. J. Med. Virol., 83: 1005–1015. doi: 10.1002/jmv.22072
- Issue published online: 18 APR 2011
- Article first published online: 18 APR 2011
- Manuscript Accepted: 27 JAN 2011
- Swiss National Science Foundation. Grant Numbers: 320000-116544, 314730-130498
- Leenaards Foundation
- French Agence Nationale pour la Recherche sur le SIDA et les Hépatites Virales (ANRS)
Glucose metabolism disturbances, including insulin resistance and type 2 diabetes, are frequent and important cofactors of hepatitis C. Increasing epidemiological and experimental data suggest that all major genotypes of hepatitis C virus (HCV), albeit to a different extent, cause insulin resistance. The HCV core protein has been shown to be sufficient to impair insulin signaling in vitro through several post-receptorial mechanisms, mostly via the activation of suppressor of cytokine signaling (SOCS) family members and the consequent decrease of insulin receptor substrate-1 (IRS-1). The levels of IRS-1 and SOCS were investigated upon expression of the core protein of HCV genotypes 1–4. Furthermore, the core protein sequences were analyzed to identify the amino acid residues responsible for IRS-1 decrease, with particular regard to SOCS mRNA deregulation. The results suggest that the activation of SOCS family members is a general mechanism associated with the common HCV genotypes. A rare genotype 1b variant, however, failed to activate any of the SOCS tested: this allowed to analyze in detail the distinct amino acid sequences responsible for SOCS deregulation. By combining approaches using intergenotypic chimeras and site-directed mutagenesis, genetic evidence was provided in favor of a role of amino acids 49 and 131 of the HCV core-encoding sequence in mediating SOCS transactivation. J. Med. Virol. 83:1005–1015, 2011. © 2011 Wiley-Liss, Inc.