Céspedes, Pablo F.Bueno, Susan M.Gomez, Roberto S.Riquelme, Sebastián A.Palavecino, Christian E.Mackern-Oberti, Juan PabloMora, Jorge E.Depoil, DavidSacristań, CatarinaCammer, MichaelCreneguy, AlisonNguyen, Tuan H.Riedel, Claudia A.Dustin, Michael L.Kalergis, Alexis M.2023-06-022023-06-022014-08Proceedings of the National Academy of Sciences of the United States of America. Volume 111, Issue 31, Pages E3214-E3223. 5 August 20140027-8424https://repositorio.unab.cl/xmlui/handle/ria/50290Indexación: ScopusHuman 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.enT lymphocyte PrimingNucleocapsid ProteincSMACpSMACArtículoAtribution 4.0 International (CC BY 4.0)DOI: 10.1073/pnas.1400760111