The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection
| Autor: | Manuel Perera-Lecoin, Ali Amara, Ophélie Dejarnac, Rasika Ramdasi, Laurent Meertens, Jiro Kitaura, Xavier Carnec, Mohamed Lamine Hafirassou, Olivier Schwartz |
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| Přispěvatelé: | Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Medical Science [tokyo], The University of Tokyo (UTokyo), Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], This study was supported by grants from the Fondation pour la Recherche Médicale and the French National Research Agency (ANR, ANR-14-CE14-0029) to A.A. This study is also supported by a public grant overseen by the ANR as part of the Investissements d'Avenir program (ANR-10-IHUB-0002). X.C., M.P.-L., and O.D. are supported by fellowships from the Fondation pour la Recherche Médicale, Total Oil and Gas Venezuela, and the Instituto Venezolano de Investigaciones Cientificas and the Ministère de la Recherche, respectively, ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] viruses media_common.quotation_subject Immunology Phosphatidylserines Dengue virus Biology Endocytosis medicine.disease_cause Microbiology Virus Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antigens CD Viral entry Virology medicine Humans Chikungunya Receptors Immunologic Internalization media_common Macrophages Phosphatidylethanolamines Membrane Proteins virus diseases Phosphatidylserine Dengue Virus Virus Internalization biochemical phenomena metabolism and nutrition Virus-Cell Interactions 3. Good health 030104 developmental biology chemistry Insect Science Host-Pathogen Interactions Receptors Virus Viral disease Chikungunya virus West Nile virus Protein Binding 030215 immunology |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2015, 90 (1), pp.92-102. ⟨10.1128/JVI.01849-15⟩ Journal of Virology, 2015, 90 (1), pp.92-102. ⟨10.1128/JVI.01849-15⟩ |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01849-15 |
| Popis: | Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection. IMPORTANCE Dengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans and is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM and TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells and mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a-dependent DENV infection relies on the direct recognition of phosphatidylethanolamine and to a lesser extent PtdSer associated with viral particles. This study provides novel insights into the mechanisms that mediate DENV entry and reinforce the concept that DENV uses an apoptotic mimicry strategy for viral entry. |
| Databáze: | OpenAIRE |
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