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

Autor: Hervouet K; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Ferrié M; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Ankavay M; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France.; Division of Gastroenterology and Hepatology, Institute of Microbiology, Lausanne, Switzerland., Montpellier C; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Camuzet C; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Alexandre V; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Dembélé A; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Lecoeur C; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Foe AT; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Bouquet P; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Hot D; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Vausselin T; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Saliou JM; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Salomé-Desnoulez S; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Vandeputte A; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Marsollier L; Université d'Angers, Nantes Université, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Angers, France., Brodin P; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France.; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR2014 - US41 - PLBS-Plateformes Lilloises de Biologie & Santé, Lille, France., Dreux M; CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm-U1111, CNRS-UMR5308, ENS-Lyon, Lyon, France., Rouillé Y; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Dubuisson J; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Aliouat-Denis CM; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France., Cocquerel L; University of Lille, CNRS, INSERM, CHU Lille, Pasteur Institute of Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, Lille, France.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Aug 25; Vol. 18 (8), pp. e1010798. Date of Electronic Publication: 2022 Aug 25 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010798
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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