RNA-Seq-based analysis of differential gene expression associated with hepatitis C virus infection in cell culture

Abstract

Hepatitis C virus (HCV) infections are one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury are still not well recognized. Thus, the identification and better characterization of host cell response to the virus infection may bring valuable insights into HCV-induced cytopathic effect and host-virus interactions. To better understand these processes we determined the changes in host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to cellular immune and metabolic response to the infection. Pathway enrichment analysis indicated that HCV induced increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism. In addition, the enrichment analyses of processes and molecular functions revealed that the up-regulated genes were implicated mainly in negative regulation of phosphorylation. The construction of the pathway-gene-process network enabled the exploration of much more complex landscape of molecular interactions. Consequently, several essential processes altered by HCV infection were identified: negative regulation of cell cycle, response to endoplasmic reticulum stress, response to reactive oxygen species, toll-like receptor signaling and pattern recognition receptor signaling. The analyses of genes whose expression was decreased upon HCV infection showed that the latter were engaged in the metabolism of lipids and amino acids. Moreover, we observed disturbance in cellular antiviral defense. Altogether, our results demonstrated that HCV infection elicits host response that includes a very wide range of cellular mechanisms.