The endocytic recycling compartment serves as a viral factory for hepatitis E virus.
Details
Serval ID
serval:BIB_AEFE49C06E94
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The endocytic recycling compartment serves as a viral factory for hepatitis E virus.
Journal
Cellular and molecular life sciences
ISSN
1420-9071 (Electronic)
ISSN-L
1420-682X
Publication state
Published
Issued date
03/12/2022
Peer-reviewed
Oui
Volume
79
Number
12
Pages
615
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
Although hepatitis E virus (HEV) is the major leading cause of enterically transmitted viral hepatitis worldwide, many gaps remain in the understanding of the HEV lifecycle. Notably, viral factories induced by HEV have not been documented yet, and it is currently unknown whether HEV infection leads to cellular membrane modeling as many positive-strand RNA viruses. HEV genome encodes the ORF1 replicase, the ORF2 capsid protein and the ORF3 protein involved in virion egress. Previously, we demonstrated that HEV produces different ORF2 isoforms including the virion-associated ORF2i form. Here, we generated monoclonal antibodies that specifically recognize the ORF2i form and antibodies that recognize the different ORF2 isoforms. One antibody, named P1H1 and targeting the ORF2i N-terminus, recognized delipidated HEV particles from cell culture and patient sera. Importantly, AlphaFold2 modeling demonstrated that the P1H1 epitope is exposed on HEV particles. Next, antibodies were used to probe viral factories in HEV-producing/infected cells. By confocal microscopy, we identified subcellular nugget-like structures enriched in ORF1, ORF2 and ORF3 proteins and viral RNA. Electron microscopy analyses revealed an unprecedented HEV-induced membrane network containing tubular and vesicular structures. We showed that these structures are dependent on ORF2i capsid protein assembly and ORF3 expression. An extensive colocalization study of viral proteins with subcellular markers, and silencing experiments demonstrated that these structures are derived from the endocytic recycling compartment (ERC) for which Rab11 is a central player. Hence, HEV hijacks the ERC and forms a membrane network of vesicular and tubular structures that might be the hallmark of HEV infection.
Keywords
Humans, Hepatitis E virus/genetics, Viral Replication Compartments, Capsid Proteins, Biological Transport, Antibodies, Monoclonal, AlphaFold2, Antibodies, Electron microscopy, Endocytic recycling compartment, Hepatitis E virus, Infectious particles, ORF2 capsid protein, Rab11, Viral factories
Pubmed
Web of science
Open Access
Yes
Create date
12/12/2022 12:38
Last modification date
23/01/2024 8:32