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An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell

Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. Hepatitis E is usually asymptomatic and self-limiting but it can become chronic in immunocompromised patients and is associated with increased fulminant hepatic failure and mortality rates in pregnant wome...

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Autores principales: Hervouet, Kévin, Ferrié, Martin, Ankavay, Maliki, Montpellier, Claire, Camuzet, Charline, Alexandre, Virginie, Dembélé, Aïcha, Lecoeur, Cécile, Foe, Arnold Thomas, Bouquet, Peggy, Hot, David, Vausselin, Thibaut, Saliou, Jean-Michel, Salomé-Desnoulez, Sophie, Vandeputte, Alexandre, Marsollier, Laurent, Brodin, Priscille, Dreux, Marlène, Rouillé, Yves, Dubuisson, Jean, Aliouat-Denis, Cécile-Marie, Cocquerel, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451086/
https://www.ncbi.nlm.nih.gov/pubmed/36007070
http://dx.doi.org/10.1371/journal.ppat.1010798
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author Hervouet, Kévin
Ferrié, Martin
Ankavay, Maliki
Montpellier, Claire
Camuzet, Charline
Alexandre, Virginie
Dembélé, Aïcha
Lecoeur, Cécile
Foe, Arnold Thomas
Bouquet, Peggy
Hot, David
Vausselin, Thibaut
Saliou, Jean-Michel
Salomé-Desnoulez, Sophie
Vandeputte, Alexandre
Marsollier, Laurent
Brodin, Priscille
Dreux, Marlène
Rouillé, Yves
Dubuisson, Jean
Aliouat-Denis, Cécile-Marie
Cocquerel, Laurence
author_facet Hervouet, Kévin
Ferrié, Martin
Ankavay, Maliki
Montpellier, Claire
Camuzet, Charline
Alexandre, Virginie
Dembélé, Aïcha
Lecoeur, Cécile
Foe, Arnold Thomas
Bouquet, Peggy
Hot, David
Vausselin, Thibaut
Saliou, Jean-Michel
Salomé-Desnoulez, Sophie
Vandeputte, Alexandre
Marsollier, Laurent
Brodin, Priscille
Dreux, Marlène
Rouillé, Yves
Dubuisson, Jean
Aliouat-Denis, Cécile-Marie
Cocquerel, Laurence
author_sort Hervouet, Kévin
collection PubMed
description Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. Hepatitis E is usually asymptomatic and self-limiting but it can become chronic in immunocompromised patients and is associated with increased fulminant hepatic failure and mortality rates in pregnant women. HEV genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Interestingly, HEV produces 3 isoforms of the ORF2 capsid protein which are partitioned in different subcellular compartments and perform distinct functions in the HEV lifecycle. Notably, the infectious ORF2 (ORF2i) protein is the structural component of virions, whereas the genome-free secreted and glycosylated ORF2 proteins likely act as a humoral immune decoy. Here, by using a series of ORF2 capsid protein mutants expressed in the infectious genotype 3 p6 HEV strain as well as chimeras between ORF2 and the CD4 glycoprotein, we demonstrated how an Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region controls the fate and functions of ORF2 isoforms. We showed that the ARM controls ORF2 nuclear translocation likely to promote regulation of host antiviral responses. This motif also regulates the dual topology and functionality of ORF2 signal peptide, leading to the production of either cytosolic infectious ORF2i or reticular non-infectious glycosylated ORF2 forms. It serves as maturation site of glycosylated ORF2 by furin, and promotes ORF2-host cell membrane interactions. The identification of ORF2 ARM as a unique central regulator of the HEV lifecycle uncovers how viruses settle strategies to condense their genetic information and hijack cellular processes.
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spelling pubmed-94510862022-09-08 An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell Hervouet, Kévin Ferrié, Martin Ankavay, Maliki Montpellier, Claire Camuzet, Charline Alexandre, Virginie Dembélé, Aïcha Lecoeur, Cécile Foe, Arnold Thomas Bouquet, Peggy Hot, David Vausselin, Thibaut Saliou, Jean-Michel Salomé-Desnoulez, Sophie Vandeputte, Alexandre Marsollier, Laurent Brodin, Priscille Dreux, Marlène Rouillé, Yves Dubuisson, Jean Aliouat-Denis, Cécile-Marie Cocquerel, Laurence PLoS Pathog Research Article Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. Hepatitis E is usually asymptomatic and self-limiting but it can become chronic in immunocompromised patients and is associated with increased fulminant hepatic failure and mortality rates in pregnant women. HEV genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Interestingly, HEV produces 3 isoforms of the ORF2 capsid protein which are partitioned in different subcellular compartments and perform distinct functions in the HEV lifecycle. Notably, the infectious ORF2 (ORF2i) protein is the structural component of virions, whereas the genome-free secreted and glycosylated ORF2 proteins likely act as a humoral immune decoy. Here, by using a series of ORF2 capsid protein mutants expressed in the infectious genotype 3 p6 HEV strain as well as chimeras between ORF2 and the CD4 glycoprotein, we demonstrated how an Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region controls the fate and functions of ORF2 isoforms. We showed that the ARM controls ORF2 nuclear translocation likely to promote regulation of host antiviral responses. This motif also regulates the dual topology and functionality of ORF2 signal peptide, leading to the production of either cytosolic infectious ORF2i or reticular non-infectious glycosylated ORF2 forms. It serves as maturation site of glycosylated ORF2 by furin, and promotes ORF2-host cell membrane interactions. The identification of ORF2 ARM as a unique central regulator of the HEV lifecycle uncovers how viruses settle strategies to condense their genetic information and hijack cellular processes. Public Library of Science 2022-08-25 /pmc/articles/PMC9451086/ /pubmed/36007070 http://dx.doi.org/10.1371/journal.ppat.1010798 Text en © 2022 Hervouet et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hervouet, Kévin
Ferrié, Martin
Ankavay, Maliki
Montpellier, Claire
Camuzet, Charline
Alexandre, Virginie
Dembélé, Aïcha
Lecoeur, Cécile
Foe, Arnold Thomas
Bouquet, Peggy
Hot, David
Vausselin, Thibaut
Saliou, Jean-Michel
Salomé-Desnoulez, Sophie
Vandeputte, Alexandre
Marsollier, Laurent
Brodin, Priscille
Dreux, Marlène
Rouillé, Yves
Dubuisson, Jean
Aliouat-Denis, Cécile-Marie
Cocquerel, Laurence
An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title_full An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title_fullStr An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title_full_unstemmed An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title_short An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell
title_sort arginine-rich motif in the orf2 capsid protein regulates the hepatitis e virus lifecycle and interactions with the host cell
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451086/
https://www.ncbi.nlm.nih.gov/pubmed/36007070
http://dx.doi.org/10.1371/journal.ppat.1010798
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