Project name: Hepacivirus C

Description: The aim of this deep sequencing project is to determine whether treatment of chronically Hepatitis C infected chimpanzees with an antiviral compound leads to accumulation of viral mutants.The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. Here, we show that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)-modified oligonucleotide (SPC3649) complementary to miR-122 leads to long-lasting suppression of HCV viremia with no evidence for viral resistance or side effects in the treated animals. Furthermore, transcriptome and histological analyses of liver biopsies demonstrated derepression of target mRNAs with miR-122 seed sites, down-regulation of interferon-regulated genes (IRGs) and improvement of HCV-induced liver pathology. The prolonged virological response to SPC3649 treatment without HCV rebound holds promise of a new antiviral therapy with a high barrier to resistance.Overall design: Animals 4x0513 and 4x0514 were chosen for analysis as the high SPC3659 concentration could induce adaptive mutations in these animals in the 5’ NCR encompassing the miR-122 seed sites. Four time points were selected, i.e. baseline (-4 weeks), end of treatment (11 weeks), first rise in viremia after treatment (17 or 23 weeks, respectively), and end of the follow-up period (end of study at 27 weeks).

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Release date: 2009-12-03

Last updated: 2009-11-06