The Blood Transcriptional Signature of Chronic Hepatitis C Virus Is Consistent with an Ongoing Interferon-Mediated Antiviral Response

Blood transcriptional profiling is a powerful tool for understanding global changes after infection, and may be useful for prognosis and prediction of drug treatment responses. This study characterizes the effects of chronic hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136-gene signature, including 66 genes elevated in infected individuals. Most of the upregulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15, and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. These genes were validated using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the upregulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of IFN-stimulated genes.