Journal
VIRUSES-BASEL
Volume 7, Issue 7, Pages 3995-4046Publisher
MDPI
DOI: 10.3390/v7072809
Keywords
HCV; glycoproteins; structure; evolution; diversity; antigenicity; functionality; vaccine
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB 900]
- German Centre for Infection Research (DZIF)
- Helmholtz Association [SO-024, HAI-IDR SO-073]
- European Research Council [ERC-2011-StG_281473-VIRAFRONT]
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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.
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