Potent neutralizing antibodies in humans infected with zoonotic simian foamy viruses target conserved epitopes located in the dimorphic domain of the surface envelope protein
In: ISSN: 1553-7366, 2018
Online
academicJournal
Zugriff:
International audience ; Human diseases of zoonotic origin are a major public health problem. Simian foamy viruses (SFVs) are complex retroviruses which are currently spilling over to humans. Replication-competent SFVs persist over the lifetime of their human hosts, without spreading to secondary hosts, suggesting the presence of efficient immune control. Accordingly, we aimed to perform an in-depth characterization of neutralizing antibodies raised by humans infected with a zoonotic SFV. We quantified the neutralizing capacity of plasma samples from 58 SFV-infected hunters against primary zoonotic gorilla and chimpanzee SFV strains, and laboratory-adapted chimpanzee SFV. The genotype of the strain infecting each hunter was identified by direct sequencing of the env gene amplified from the buffy coat with genotype-specific primers. Foamy virus vector particles (FVV) enveloped by wild-type and chimeric gorilla SFV were used to map the envelope region targeted by antibodies. Here, we showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. Neutralizing antibodies target the dimorphic portion of the envelope protein surface domain. Epitopes recognized by neutralizing antibodies have been conserved during the cospeciation of SFV with their nonhuman primate host. Greater neutralization breadth in plasma samples of SFV-infected humans was statistically associated with smaller SFV-related hematological changes. The neutralization patterns provide evidence for persistent expression of viral proteins and a high prevalence of coinfection. In conclusion, neutralizing antibodies raised against zoonotic SFV target immunodominant and conserved epitopes located in the receptor binding domain. These properties support their potential role in restricting the spread of SFV in the human population.
| Titel: |
Potent neutralizing antibodies in humans infected with zoonotic simian foamy viruses target conserved epitopes located in the dimorphic domain of the surface envelope protein
|
|---|---|
| Autor/in / Beteiligte Person: | Lambert, Caroline ; Couteaudier, Mathilde ; Gouzil, Julie ; Richard, Léa ; Montange, Thomas ; Betsem, Edouard ; Rua, Rejane ; Tobaly-Tapiero, Joelle ; Lindemann, Dirk ; Njouom, Richard ; Gessain, Antoine ; Mouinga-Ondemé, Augustin ; Buseyne, Florence ; Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)) ; Institut Pasteur Paris (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS) ; Pasteur, Cellule ; Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité ; 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)-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) ; Institute of Virology Dresden ; Technische Universität Dresden = Dresden University of Technology (TU Dresden) ; Centre Pasteur du Cameroun ; Réseau International des Instituts Pasteur (RIIP) ; Centre International de Recherches Médicales de Franceville (CIRMF) ; CL was personally supported by a doctoral grant from the French government program Investissement d'Avenir, Laboratory of Excellence, Integrative Biology of Emerging Infectious Diseases (LabEx IBEID, http://www.agence-nationale-recherche.fr/ProjetIA-10-LABX-0062). LR was personally supported by the Bourse de l’Ecole Normale Supérieure, Faculté Paris Diderot, http://www.ens.fr/. This work was supported by the Institut Pasteur in Paris, France, the Programme Transversal de Recherche from the Institut Pasteur PTR#437 , https://www.pasteur.fr/fr, and the Agence Nationale de la Recherche grant ANR-10-LABX-62-IBEID ; http://www.agence-nationale-recherche.fr/ProjetIA-10-LABX-0062 ; REEMFOAMY project, ANR 15-CE-15-0008-01 ; http://www.agence-nationale-recherche.fr/projet-anr/?tx_lwmsuivibilan_pi2%5BCODE%5D=ANR-15-CE15-0008 . The work in the laboratory of DL is supported by the Deutsche Forschungsgemeinschaft DFG, German Research Foundation grants LI 621/10-1, SPP1923 LI 621/11-1, http://www.dfg.de/ . The funding agencies had no role in the study design, generation of results, or writing of the manuscript. ; We thank P. Souque, C. Blanc, and P. Afonso for their helpful advice on the molecular biology experiments. We are indebted to Pascale Lesage, Alessia Zamborlini, Ali Saïb, and Olivier Schwartz for helpful discussions. We thank members from the EPVO research unit for discussions and technical advices. ; ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010) ; ANR-15-CE15-0008,REEMFOAMY,L'infection humaine par les virus foamy simiens zoonotiques : rôle des facteurs virologiques et immunologiques dans la restrcition de l'emergence virale(2015) |
| Link: | |
| Zeitschrift: | ISSN: 1553-7366, 2018 |
| Veröffentlichung: | HAL CCSD ; Public Library of Science, 2018 |
| Medientyp: | academicJournal |
| DOI: | 10.1371/journal.ppat.1007293 |
| Schlagwort: |
|
| Sonstiges: |
|