title: Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design.
abstract: In the 26 years since the discovery of Hepatitis C virus (HCV) a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA) regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design.
authors.affiliation: School of Life Sciences, Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham NG7 2RD, UK. alex.tarr@nottingham.ac.uk.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Tarr
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. tanvi.khera@twincore.de.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Khera
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. kathrin.hueging@twincore.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hueging
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. julie.sheldon@twincore.de.
authors.forename: Julie
authors.initials: J
authors.lastname: Sheldon
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. eike.steinmann@twincore.de.
authors.forename: Eike
authors.initials: E
authors.lastname: Steinmann
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. thomas.pietschmann@twincore.de.|German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Braunschweig 38124, Germany. thomas.pietschmann@twincore.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
authors.affiliation: Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centrefor Infection Research (HZI), Hannover D-30625, Germany. richard.brown@twincore.de.
authors.forename: Richard J P
authors.initials: RJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D014644:Genetic Variation; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
chemical_list: D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines
keywords: HCV; antigenicity; diversity; evolution; functionality; glycoproteins; structure; vaccine