High-throughput approaches to unravel hepatitis C virus-host interactions

Virus Res. 2016 Jun 15;218:18-24. doi: 10.1016/j.virusres.2015.09.013. Epub 2015 Sep 26.


Hepatitis C virus (HCV) remains a major global health burden, with more than 130 million individuals chronically infected and at risk for the development of hepatocellular carcinoma (HCC). The recent clinical licensing of direct-acting antivirals enables viral cure. However, limited access to therapy and treatment failure in patient subgroups warrants a continuing effort to develop complementary antiviral strategies. Furthermore, once fibrosis is established, curing HCV infection does not eliminate the risk for HCC. High-throughput approaches and screens have enabled the investigation of virus-host interactions on a genome-wide scale. Gain- and loss-of-function screens have identified essential host-dependency factors in the HCV viral life cycle, such as host cell entry factors or regulatory factors for viral replication and assembly. Network analyses of systems-scale data sets provided a comprehensive view of the cellular state following HCV infection, thus improving our understanding of the virus-induced responses of the target cell. Interactome, metabolomics and gene expression studies identified dysregulated cellular processes potentially contributing to HCV pathogenesis and HCC. Drug screens using chemical libraries led to the discovery of novel antivirals. Here, we review the contribution of high-throughput approaches for the investigation of virus-host interactions, viral pathogenesis and drug discovery.

Keywords: HCV pathogenesis; Hepatitis C virus; Systems biology; Virus-host interactions.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / therapeutic use
  • Claudins / genetics
  • Claudins / metabolism
  • Ephrin-A2 / genetics
  • Ephrin-A2 / metabolism
  • Gene Expression Regulation
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepacivirus / growth & development
  • Hepacivirus / pathogenicity
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • High-Throughput Screening Assays
  • Host-Pathogen Interactions*
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / virology
  • Occludin / genetics
  • Occludin / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, EphA2
  • Signal Transduction
  • Systems Biology / methods*
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Claudins
  • EPHA2 protein, human
  • Ephrin-A2
  • OCLN protein, human
  • Occludin
  • Viral Proteins
  • Receptor, EphA2
  • NUAK2 protein, human
  • Protein Serine-Threonine Kinases