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.
Highlights
Discovered as the causative agent of non-A non-B hepatitis in 1989 [1], the hepatitis C virus (HCV) is a member of the genus Hepacivirus
The structural proteins include the viral capsid encoded by the core coding-region and the envelope glycoproteins E1 and E2 encoded by the E1 and E2 coding-regions
In this review we summarize current knowledge of all aspects of HCV glycoprotein biology, including structure, genetic diversity, antigenicity and functionality, in addition to the current status of potential vaccination strategies
Summary
Discovered as the causative agent of non-A non-B hepatitis in 1989 [1], the hepatitis C virus (HCV) is a member of the genus Hepacivirus. They are heavily glycosylated with complex sugar moieties and represent the key determinants for HCV entry into permissive cells, facilitating receptor binding and mediating the fusion process between viral envelope and endosomal host cell membrane. The proteins contribute to virion assembly, bind host lipoproteins and interfere with host innate immune responses. While these critical functions must be maintained, HCV glycoproteins are the targets of host adaptive immune surveillance and must evolve to escape detection, which is facilitated by the error-prone nature of viral replication. In this review we summarize current knowledge of all aspects of HCV glycoprotein biology, including structure, genetic diversity, antigenicity and functionality, in addition to the current status of potential vaccination strategies
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