title: Interferon-α inducible protein 6 impairs EGFR activation by CD81 and inhibits hepatitis C virus infection.
abstract: Viral entry requires co-operative interactions of several host cell factors. Interferon (IFN) and the IFN-stimulated genes (ISGs) play a central role in antiviral responses against hepatitis C virus (HCV) infection. We examined the effect of interferon-α inducible protein 6 (IFI6) against HCV infection in human hepatoma cells. HCV RNA level or infectious foci were inhibited significantly by ectopic expression of IFI6. IFI6 impaired CD81 co-localization with claudin-1 (CLDN1) upon HCV infection or CD81 cross-linking by specific antibody. Activation of epidermal growth factor receptor (EGFR), a co-factor involved in CD81/CLDN1 interactions, was reduced in IFI6 expressing cells in response to HCV infection or CD81 cross linking by antibody, but not by treatment with EGF. Taken together, the results from our study support a model where IFI6 inhibits HCV entry by impairing EGFR mediated CD81/CLDN1 interactions. This may be relevant to other virus entry processes employing EGFR.
authors.affiliation: Department of Internal Medicine, Saint Louis University.
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine, Saint Louis University.
authors.forename: Young-Chan
authors.initials: YC
authors.lastname: Kwon
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1] Department of Medicine and Genetics, University of Arkansas for Medical Sciences [2] The Central Arkansas Veterans Healthcare System.
authors.forename: Curt H
authors.initials: CH
authors.lastname: Hagedorn
authors.affiliation: 1] Department of Internal Medicine, Saint Louis University [2] Department of Pathology, Saint Louis University.
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
authors.affiliation: 1] Department of Internal Medicine, Saint Louis University [2] Department of Molecular Microbiology &Immunology, Saint Louis University.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction; D060225:Tetraspanin 28 / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication; D018631:ras Proteins / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; C406887:IFI27 protein, human; C468762:IFI6 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D060225:Tetraspanin 28; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins