The human respiratory syncytial virus nucleoprotein is expressed on the surface of dendritic cells and inhibits immunological synapse assembly by T cells (VIR2P.1018)

Abstract

Abstract 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 prime antigen-specific naïve T cells, a process needed to mount a proper antiviral immune response and eliminate hRSV from the airways. 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 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 well as with reduced phosphorylation of tyrosine residues in the interacting pole of 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.