PMID (identifiant
de la référence Pubmed) : |
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 (21775467) |
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| Titre : |
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Anti-SARS-CoV Spike Antibodies Trigger Infection of Human Immune Cell via a pH- and Cysteine Protease-Independent Fc{gamma}R Pathway. |
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| Auteur(s) : |
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Martial Jaume ( ) 1, Ming S Yip1, Chung Y Cheung2, Hiu L Leung1, Ping H Li1, Francois Kien1, Isabelle Dutry1, 2, Nicolas Escriou3, Ralf Altmeyer1, 4, Beatrice Nal1, 5, Marc Daëron6, Roberto Bruzzone1, J S Malik Peiris1, 2 |
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| Laboratoire : |
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| Résumé : |
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Public health measures successfully contained outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV). However, the precursor of the SARS-CoV remains in its natural bat reservoir and re-emergence of a human-adapted SARS-like coronavirus remains a plausible public health concern. Vaccination is a major strategy for containing resurgence of SARS in humans and a number of vaccine candidates have been tested in experimental animal models. We previously reported that antibody elicited by a SARS-CoV vaccine candidate based on recombinant full-length Spike-protein trimers potentiated infection of human B cell lines despite eliciting in vivo a neutralizing and protective immune response in rodents. These observations prompted us to investigate the mechanisms underlying antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro. Here we demonstrate that anti-Spike immune serum, while inhibiting viral entry in a permissive cell line, potentiated infection of immune cells by SARS-CoV Spike-pseudotyped lentiviral particles as well as replication-competent SARS coronavirus. Antibody-mediated infection was dependent on Fcγ receptor II but did not use the endosomal/lysosomal pathway utilized by angiotensin I converting enzyme 2 (ACE2), the accepted receptor for SARS-CoV. This suggests that ADE of SARS-CoV utilizes a novel cell entry mechanism into immune cells. Different SARS vaccine candidates elicit sera that differ in their capacity to induce ADE in immune cells, in spite of comparable potency to neutralize infection in ACE2-bearing cells. Our results suggest a novel mechanism by which SARS-CoV can enter target cells and illustrate potential pitfalls associated with immunization against it. They should prompt further investigations into SARS pathogenesis. |
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| Domaine : |
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Sciences du Vivant/Microbiologie et Parasitologie/Virologie
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Langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1098-5514 |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1128/JVI.00671-11 |
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| Journal : |
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| Journal of Virology (J Virol) |
| Publisher |
American Society for Microbiology |
| ISSN |
0022-538X |
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| Audience : |
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internationale |
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| Date de publication : |
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20/07/2011 |
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Date de publication
électronique : |
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20/07/2011 |
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| Page, identifiant, ... : |
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epub ahead of print |
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| Contrat, financement : |
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This work was supported by the Research Fund for the Control of Infectious Disease (RFCID; projects no. 05050182 and 09080872) of the Hong Kong Government and by the RESPARI project of the Institut Pasteur International Network. |
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