Academic Journal
The AP-1 adaptor complex is essential for intracellular trafficking of the ORF2 capsid protein and assembly of Hepatitis E virus
| العنوان: | 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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| المؤلفون: | Ferrié, Martin, Alexandre, Virginie, Montpellier, Claire, Bouquet, Peggy, Tubiana, Thibault, Mézière, Léa, Ankavay, Maliki, Bentaleb, Cyrine, Dubuisson, Jean, Bressanelli, Stéphane, Rouillé, Yves, Aliouat-Denis, Cécile-Marie, Cocquerel, Laurence |
| المساهمون: | Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Microbiologie clinique Lille, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institute of Microbiology University of Lausanne (IMUL), Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV), MF was supported by a fellowship from the Institut Pasteur de Lille, the Région Hauts-de-France and the ANRS-Maladies infectieuses émergentes (ANRS-MIE). TT was supported by a postdoctoral fellowship from ANRS-MIE. LM is currently supported by a Région Hauts-de-France/University of Lille fellowship. MA was supported by ANRS-MIE and is currently supported by the Fonds National Suisse (FNS). CB was supported by ANRS-MIE, INSERM-Transfert, Région Hauts-de-France and Institut Pasteur de Lille. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. |
| المصدر: | ISSN: 1420-682X. |
| بيانات النشر: | CCSD Springer Verlag |
| سنة النشر: | 2024 |
| المجموعة: | Réseau International des Instituts Pasteur, Paris: HAL-RIIP |
| مصطلحات موضوعية: | Replication, A5 membrane traffic inhibitor, PLC3 cells, Primary human hepatocytes, Proximity ligation assay, P1H1 antibody, P3H2 antibody, AlphaFold2, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/39117755; PUBMED: 39117755; PUBMEDCENTRAL: PMC11335258 |
| DOI: | 10.1007/s00018-024-05367-0 |
| الاتاحة: | https://hal.science/hal-04730214 https://hal.science/hal-04730214v1/document https://hal.science/hal-04730214v1/file/Ferrie%CC%81-The%20AP-1%20adaptor%20complex%20is%20essential%20for%20intracellular%20trafficking%20of%20the%20ORF2%20capsid%20protein%20and%20assembly%20of%20Hepatitis%20E%20virus-2024-Cellular%20and%20Molecular%20Life%20Sciences.pdf https://doi.org/10.1007/s00018-024-05367-0 |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.E6B99AC4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00018-024-05367-0 |
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