title: Discovery of cellular proteins required for the early steps of HCV infection using integrative genomics.
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.
authors.affiliation: Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Solip
authors.initials: S
authors.lastname: Park
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.forename: Oh Sung
authors.initials: OS
authors.lastname: Kwon
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
mesh_terms: D015894:Genome, Human / Q000235:genetics; D023281:Genomics / Q000379:methods*; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D060149:Tetraspanin 30 / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D011506:Proteins; D060149:Tetraspanin 30; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus