Abstract
Hepatitis C virus (HCV) encodes two envelope glycoproteins, E1 and E2. Their structure and mode of fusion remain unknown, and so does the virion architecture. The organization of the HCV envelope shell in particular is subject to discussion as it incorporates or associates with host-derived lipoproteins, to an extent that the biophysical properties of the virion resemble more very-low-density lipoproteins than of any virus known so far. The recent development of novel cell culture systems for HCV has provided new insights on the assembly of this atypical viral particle. Hence, the extensive E1E2 characterization accomplished for the last two decades in heterologous expression systems can now be brought into the context of a productive HCV infection. This review describes the biogenesis and maturation of HCV envelope glycoproteins, as well as the interplay between viral and host factors required for their incorporation in the viral envelope, in a way that allows efficient entry into target cells and evasion of the host immune response.
Highlights
Discovered in 1989, hepatitis C virus infects 3% of the world population [1]
The difficulty to image assembly events has led to the optimization of indirect assays to evaluate the different steps of assembly, including virus envelopment and the incorporation of E1 and E2 glycoproteins
Larger-scale purification of the virion-embedded glycoprotein complexes will help understanding the organization of the virion outer shell, how large complexes can be built from heterodimers and why they might need priming for entry
Summary
Discovered in 1989, hepatitis C virus infects 3% of the world population [1]. Associated with an 80% chronicity rate, the virus is responsible for liver disease, evolving from liver fibrosis and cirrhosis to hepatocellular carcinoma [2]. Members of the Flaviviridae family share a common genomic organization Their short positive-strand RNA genome encodes a single polyprotein, which serves as a precursor for the structural and non-structural proteins. NS3 to 5B are necessary and sufficient for the viral RNA replication [4] They are involved, together with p7, NS2 and the structural proteins, in the assembly of progeny virions [5]. The mature gene products carry out RNA replication, in association with ER- (endoplasmic reticulum) derived membranes, and the assembly of progeny virions, which travel through the secretory pathway before secretion and infection of naive cells. This review summarizes our current understanding of HCV glycoprotein incorporation into the viral envelope, from their biogenesis in the ER until their exposure onto the virion surface as functional entry units
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