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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9451086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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