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- W4241946216 abstract "Event Abstract Back to Event Surface expression of human Respiratory Syncytial Virus (hRSV) Nucleoprotein inhibits immunological synapse assembly by T cells Pablo F. Céspedes1, 2*, Susan M. Bueno1, 2, Bruno A. Ramirez1, 2, Roberto S. Gómez1, 2, Sebastián A. Riquelme1, 2, 3, Christian E. Palavecino1, 2, Juan P. Mackern-Oberti1, 2, Jorge Mora1, 2, David Depoil4, 5, Catarina Sacristán4, Michael Cammer4, Alison Creneguy3, Tuan H. Nguyen3, Claudia A. Riedel2, 6, Michael L. Dustin4, 5 and Alexis M. Kalergis1, 2, 7* 1 Pontificia Universidad Católica de Chile, Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Chile 2 Millennium Institute on Immunology and Immunotherapy, Chile 3 INSERM, U1064, France 4 New York University, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, United States 5 University of Oxford, Kennedy Institute of Rheumatology, United Kingdom 6 Universidad Nacional Andrés Bello, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina,, Chile 7 Pontificia Universidad Católica de Chile, Facultad de Medicina, Departamento de Inmunología Clínica y Reumatología, Chile The human Respiratory Syncytial Virus (hRSV) is the major cause of children severe respiratory tract infections worldwide. Both, the poor activation of T cells and the limited generation of memory T cells following disease resolution are considered key processes favoring hRSV epidemics, which are based on re-infections. It is known that hRSV infects Dendritic cells (DCs) dampening their capacity to activate naïve T cells, a critical process in the initiation, expansion and establishment of proper antiviral immune responses. Here we show that the hRSV nucleoprotein (N) is expressed at the surface of a variety of infected cells, including DCs. After estimating the approximate density of N in the surface of DCs and other cells, we evaluated whether these physiological densities could affect the assembly of the immunological synapse (IS) by naïve and antigen-experienced CD4+ T cells. We observed that N, but not control proteins inhibited the assembly of IS by interfering with TCR-pMHC interactions, which was accompanied with reduced accumulation of TCR and reduced central clustering of pMHC at the T cell-bilayer interface. As expected, reduced synapse assembly, as well as reduced pMHC and TCR accumulation was associated with a consequent reduction in the phosphorylation of tyrosine residues in the interacting surface of the stimulated T cells. Similarly, either DCs transduced with lentivirus encoding hRSV N or DCs loaded with purified N protein failed at inducing the up-regulation of the TCR-driven activation marker CD69 in stimulated T cells. Altogether, our findings propose N-hRSV as a key virulence factor responsible for the suboptimal T cell activation observed in hRSV-infected individuals and the poor acquisition of memory T cell responses following disease resolution. Acknowledgements This research was supported by CONICYT grants FONDECYT POSTDOCTORADO N° 3140455, and by FONDECYT grant 1070352; FONDEF D061008; and the Millennium Institute on Immunology and Immunotherapy (P07/088-F) and grant “Nouvelles Equipes-nouvelles thématiques” from the La Région Pays De La Loire and the Evaluation-Orientation of Scientific Cooperation France-Chile grant. Keywords: T cell priming, memory T cells, TCR signaling, cSMAC, pSMAC, Nucleocapsid protein, Ribonucleoproteins, Human Respiratory Syncytial Virus A Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Oral Presentation Topic: Adaptive Immunity Citation: Céspedes PF, Bueno SM, Ramirez BA, Gómez RS, Riquelme SA, Palavecino CE, Mackern-Oberti JP, Mora J, Depoil D, Sacristán C, Cammer M, Creneguy A, Nguyen TH, Riedel CA, Dustin ML and Kalergis AM (2015). Surface expression of human Respiratory Syncytial Virus (hRSV) Nucleoprotein inhibits immunological synapse assembly by T cells. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00315 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Apr 2015; Published Online: 15 Sep 2015. * Correspondence: Dr. Pablo F Céspedes, Pontificia Universidad Católica de Chile, Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Santiago, RM, 8331150, Chile, pfcespedes@icloud.com Dr. Alexis M Kalergis, Pontificia Universidad Católica de Chile, Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Santiago, RM, 8331150, Chile, akalergis@bio.puc.cl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Pablo F Céspedes Susan M Bueno Bruno A Ramirez Roberto S Gómez Sebastián A Riquelme Christian E Palavecino Juan P Mackern-Oberti Jorge Mora David Depoil Catarina Sacristán Michael Cammer Alison Creneguy Tuan H Nguyen Claudia A Riedel Michael L Dustin Alexis M Kalergis Google Pablo F Céspedes Susan M Bueno Bruno A Ramirez Roberto S Gómez Sebastián A Riquelme Christian E Palavecino Juan P Mackern-Oberti Jorge Mora David Depoil Catarina Sacristán Michael Cammer Alison Creneguy Tuan H Nguyen Claudia A Riedel Michael L Dustin Alexis M Kalergis Google Scholar Pablo F Céspedes Susan M Bueno Bruno A Ramirez Roberto S Gómez Sebastián A Riquelme Christian E Palavecino Juan P Mackern-Oberti Jorge Mora David Depoil Catarina Sacristán Michael Cammer Alison Creneguy Tuan H Nguyen Claudia A Riedel Michael L Dustin Alexis M Kalergis PubMed Pablo F Céspedes Susan M Bueno Bruno A Ramirez Roberto S Gómez Sebastián A Riquelme Christian E Palavecino Juan P Mackern-Oberti Jorge Mora David Depoil Catarina Sacristán Michael Cammer Alison Creneguy Tuan H Nguyen Claudia A Riedel Michael L Dustin Alexis M Kalergis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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- W4241946216 title "Surface expression of human Respiratory Syncytial Virus (hRSV) Nucleoprotein inhibits immunological synapse assembly by T cells" @default.
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