title: RNA-Seq-based analysis of differential gene expression associated with hepatitis C virus infection in a cell culture.
abstract: Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an 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 mainly implicated in the negative regulation of phosphorylation. Construction of the pathway-gene-process network enabled exploration of a 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 the cellular antiviral defense. Altogether, our results demonstrated that HCV infection elicits host response that includes a very wide range of cellular mechanisms. Our findings significantly broaden the understanding of complex processes that accompany HCV infection. Consequently, they may be used for developing new host-oriented therapeutic strategies.
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
authors: Anna
authors: A
authors: Hojka-Osinska
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
authors: Lucyna
authors: L
authors: Budzko
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland; Institute of Computing Science, Poznan University of Technology, Poznań, Poland.
authors: Agnieszka
authors: A
authors: Zmienko
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland; Institute of Computing Science, Poznan University of Technology, Poznań, Poland.
authors: Agnieszka
authors: A
authors: Rybarczyk
authors: Institut Pasteur, Unité Hepacivirus et Immunité Innée, CNRS, URA 3015, Département de Virologie, Paris, France.
authors: Patrick
authors: P
authors: Maillard
authors: Institut Pasteur, Unité Hepacivirus et Immunité Innée, CNRS, URA 3015, Département de Virologie, Paris, France.
authors: Agata
authors: A
authors: Budkowska
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland; Institute of Computing Science, Poznan University of Technology, Poznań, Poland.
authors: Marek
authors: M
authors: Figlerowicz
authors: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland; Institute of Chemical Technology and Engineering, Poznan University of Technology, Poznań, Poland.
authors: Paulina
authors: P
authors: Jackowiak
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D053858:Metabolic Networks and Pathways; D017423:Sequence Analysis, RNA; D059467:Transcriptome