Hepatitis C virus (HCV) research has been restricted by the absence of an animal model that recapitulates HCV pathophysiology. Recent studies demonstrate that Norway rat hepacivirus, RHV-rn1, is genetically close to HCV and chronically infects fully immunocompetent rats. Furthermore, chronic RHV-rn1 infection in Sprague Dawley rats induce chronic viremia and liver steatosis resembling HCV infection in humans. To investigate whether a high-fat, high-sugar diet could aggravate virus-induced dysregulation of hepatic metabolism, a “Western diet” (WD) was administered for 8 weeks to RHV-rn1 chronically infected rats.
Four groups (NI-ND: noninfected fed normal diet, I-ND: infected fed normal diet, NI-WD: noninfected fed WD, and I-WD: infected fed WD), each composed of twelve Sprague Dawley rats, were followed for 30 weeks post RHV-rn1 challenge. We aim to investigate the liver transcriptome of these four groups of rats. Particularly, we would like to identify differentially expressed genes as well as dysregulated metabolic pathways in the following comparisons:
1. NI-ND vs. I-ND: Dysregulated genes/pathways due to chronic RHV-rn1 infection
2. NI-ND vs. NI-WD: Dysregulated genes/pathways due to Western diet
3. I-ND vs. I-WD: Additive or synergistic dysregulation caused by the Western diet imposed on established chronic RHV-rn1 infection
