Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics

PLoS One. 2013 Apr 12;8(4):e60333. doi: 10.1371/journal.pone.0060333. Print 2013.

Abstract

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genome, Human / genetics
  • Genomics / methods*
  • Hepacivirus / physiology*
  • Hepatitis C / virology*
  • Humans
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Reproducibility of Results
  • Tetraspanin 30 / metabolism
  • Viral Envelope Proteins / metabolism
  • Virus Internalization

Substances

  • Proteins
  • Tetraspanin 30
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus

Grant support

This work is supported by NRF BRL [2010-0019706] and WCU program through the NRF [R31-2008-10105] funded by the Korea government (MEST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.