Respiratory Syncytial Virus Interferon Antagonist NS1 Protein Suppresses and Skews the Human T Lymphocyte Response
Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract disease.
Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract disease. The virus has two IFN-I antagonist proteins, NS1 and NS2. In this study, primary human dendritic cells were infected with recombinant RSV from which the NS1 and/or the NS2 genes were deleted. The effects on the proliferation of autologous T lymphocytes during co-culture was then evaluated in vitro. Deletion of the NS1, but not NS2, protein resulted in three major effects: (i) an increased activation and proliferation of CD8+ T cells that express CD103, a tissue homing integrin that directs CD8+ T cells to mucosal epithelial cells of the respiratory tract and triggers cytolytic activity; (ii) an increased activation and proliferation of Th17 cells, which have recently been shown to have anti-viral effects and also indirectly attract neutrophils; and (iii) decreased activation of IL-4-producing CD4+ T cells - which are associated with enhanced RSV disease - and reduced proliferation of total CD4+ T cells. They were also able to show that these effects are not due to suppressed IFN-I production or signaling in dendritic cells or T cells, and that they likely result from reduced maturation of dendritic cells caused by the NS1 protein.
