Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

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dc.contributor.authorCéspedes, Pablo F.
dc.contributor.authorBueno, Susan M.
dc.contributor.authorGomez, Roberto S.
dc.contributor.authorRiquelme, Sebastián A.
dc.contributor.authorPalavecino, Christian E.
dc.contributor.authorMackern-Oberti, Juan Pablo
dc.contributor.authorMora, Jorge E.
dc.contributor.authorDepoil, David
dc.contributor.authorSacristań, Catarina
dc.contributor.authorCammer, Michael
dc.contributor.authorCreneguy, Alison
dc.contributor.authorNguyen, Tuan H.
dc.contributor.authorRiedel, Claudia A.
dc.contributor.authorDustin, Michael L.
dc.contributor.authorKalergis, Alexis M.
dc.date.accessioned2023-06-02T17:51:45Z
dc.date.available2023-06-02T17:51:45Z
dc.date.issued2014-08
dc.descriptionIndexación: Scopuses
dc.description.abstractHuman respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse- and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4+ T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell−bilayer interface, suggesting that N protein interferes with pMHC−TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV.es
dc.description.urihttps://www.pnas.org/doi/full/10.1073/pnas.1400760111
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America. Volume 111, Issue 31, Pages E3214-E3223. 5 August 2014es
dc.identifier.doiDOI: 10.1073/pnas.1400760111
dc.identifier.issn0027-8424
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/50290
dc.language.isoenes
dc.publisherNational Academy of Scienceses
dc.rights.licenseAtribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectT lymphocyte Priminges
dc.subjectNucleocapsid Proteines
dc.subjectcSMACes
dc.subjectpSMACes
dc.titleSurface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cellses
dc.typeArtículoes
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