The hepatitis C virus (HCV) p7 viroporin modulates the cell secretory pathway and determines HCV specific infectivity

The hepatitis C virus (HCV) p7 viroporin modulates the cell secretory pathway and determines HCV specific infectivity

 

Viroporins are small transmembrane viral proteins with ion channel activities modulating properties of intracellular membranes, which impacts several fundamental biological processes such as trafficking, ion fluxes as well as connections and exchanges between organelles. Hepatitis C virus (HCV) encodes a viroporin, p7, acting during assembly, envelopment and secretion of viral particles. HCV p7 is produced by cleavage from the HCV polyprotein but also exists as an E2p7 precursor, of poorly defined properties. In this study, we have explored how the retarded cleavage between E2 glycoprotein and p7 viroporin could regulate their functions associated to virion assembly and/or perturbation of cellular membrane processes. Specifically, we demonstrate that p7 is able to regulate the cell secretory pathway, which induces the intracellular retention of HCV glycoproteins and favors assembly of HCV particles. Our study also identifies a novel assembly function located at p7 amino-terminus that is unmasked through E2p7-regulated processing and that controls the infectivity of different types of released viral particles. Altogether, our results underscore a critical post-translational control of assembly and secretion of HCV particles that governs their specific infectivity.

 

Citation: Denolly S, Mialon C, Bourlet T, Amirache F, Penin F, Lindenbach B, et al. (2017) The amino-terminus of the hepatitis C virus (HCV) p7 viroporin and its cleavage from glycoprotein E2-p7 precursor determine specific infectivity and secretion levels of HCV particle types. PLoS Pathog 13(12):e1006774. https://doi.org/10.1371/journal.ppat.1006774

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