Respiratory syncytial virus interferon antagonist NS1 protein suppresses and skews the human T lymphocyte response

PLoS Pathog. 2011 Apr;7(4):e1001336. doi: 10.1371/journal.ppat.1001336. Epub 2011 Apr 21.


We recently demonstrated that the respiratory syncytial virus (RSV) NS1 protein, an antagonist of host type I interferon (IFN-I) production and signaling, has a suppressive effect on the maturation of human dendritic cells (DC) that was only partly dependent on released IFN-I. Here we investigated whether NS1 affects the ability of DC to activate CD8+ and CD4+ T cells. Human DC were infected with RSV deletion mutants lacking the NS1 and/or NS2 genes and assayed for the ability to activate autologous T cells in vitro, which were analyzed by multi-color flow cytometry. 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. Except for total CD4+ T cell proliferation, none of the T cell effects appeared to be due to increased IFN-I signaling. In the infected DC, deletion of the NS1 and NS2 genes strongly up-regulated the expression of cytokines and other molecules involved in DC maturation. This was partly IFN-I-independent, and thus might account for the T cell effects. Taken together, these data demonstrate that the NS1 protein suppresses proliferation and activation of two of the protective cell populations (CD103+ CD8+ T cells and Th17 cells), and promotes proliferation and activation of Th2 cells that can enhance RSV disease.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Female
  • Humans
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism
  • Interferons / antagonists & inhibitors*
  • Interferons / genetics
  • Interferons / immunology
  • Interferons / metabolism
  • Male
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation / genetics
  • Up-Regulation / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*
  • Viral Nonstructural Proteins / metabolism


  • Antigens, CD
  • Cytokines
  • Integrin alpha Chains
  • Viral Nonstructural Proteins
  • alpha E integrins
  • Interferons