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Cited by 10Hepatitis Viruses Studies and EpidemiologyCellular transport and secretionHepatitis B Virus Studies

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The AP-1 adaptor complex is essential for intracellular trafficking of the ORF2 capsid protein and assembly of Hepatitis E virus

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Ferrié, Martin, Alexandre, Virginie, Montpellier, Claire, Bouquet, Peggy, Tubiana, Thibault, Mézière, Léa, Ankavay, Maliki, Bentaleb, Cyrine, Dubuisson, Jean, Bressanelli, Stéphane, Aliouat-Denis, Cécile-Marie, Rouillé, Yves, Cocquerel, Laurence·2024·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-024-05367-0PMC PMC11335258

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Abstract

Although the Hepatitis E virus (HEV) is an emerging global health burden, little is known about its interaction with the host cell. HEV genome encodes three proteins including the ORF2 capsid protein that is produced in different forms, the ORF2i protein which is the structural component of viral particles, and the ORF2g/c proteins which are massively secreted but are not associated with infectious material. We recently demonstrated that the endocytic recycling compartment (ERC) is hijacked by HEV to serve as a viral factory. However, host determinants involved in the subcellular shuttling of viral proteins to viral factories are unknown. Here, we demonstrate that the AP-1 adaptor complex plays a pivotal role in the targeting of ORF2i protein to viral factories. This complex belongs to the family of adaptor proteins that are involved in vesicular transport between the trans-Golgi network and early/recycling endosomes. An interplay between the AP-1 complex and viral protein(s) has been described for several viral lifecycles. In the present study, we demonstrated that the ORF2i protein colocalizes and interacts with the AP-1 adaptor complex in HEV-producing or infected cells. We showed that silencing or drug-inhibition of the AP-1 complex prevents ORF2i protein localization in viral factories and reduces viral production in hepatocytes. Modeling of the ORF2i/AP-1 complex also revealed that the S domain of ORF2i likely interacts with the σ1 subunit of AP-1 complex. Hence, our study identified for the first time a host factor involved in addressing HEV proteins (i.e. ORF2i protein) to viral factories.

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Metadata

Authors
Ferrié, M., Alexandre, V., Montpellier, C., Bouquet, P., Tubiana, T., Mézière, L., Ankavay, M., Bentaleb, C., Dubuisson, J., Bressanelli, S., Aliouat-Denis, C.-M., Rouillé, Y., & Cocquerel, L.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Institut Pasteur de Lille (FR)
Corresponding author
Cocquerel, Laurence
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2024-08-09
Volume
81
Issue
1
Pages
335-335
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-024-05367-0
PMC
PMC11335258
OpenAlex
W4401455876
Cited by
10
References
1
Citations by year
2026: 2 · 2025: 8
FWCI
2.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • IRIS (submittedVersion, cc-by-nc-nd)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • Institut Pasteur de Lille (Institut Pasteur de Lille, HEV-Cure)
  • Région Hauts-de-France (Région Hauts-de-France, HEV-Cure)
  • Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ECTZ205629, ECTZ189696, AAP 2015-2, ECTZ74553, AAP 2015-2, ECTZ61515)
  • Inserm-Transfert (HEV-Cure)
  • Université de Lille (Université de Lille)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatitis Viruses Studies and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
hepatitis E virus, ORF2 capsid protein, viral assembly, intracellular trafficking, recycling endosomes, viral factories, host-virus interaction, trans-Golgi network, early endosomes, S domain, hepatocytes
MeSH terms
Humans, Viral Proteins, Hepatitis E, Hepatitis E virus, Virus Assembly, Protein Transport, Adaptor Protein Complex 1, Capsid Proteins

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