Induction of interferon-alpha and tumor necrosis factor-related apoptosis-inducing ligand in human blood mononuclear cells by hemagglutinin-neuraminidase but not F protein of Newcastle disease virus

Abstract

To determine molecular viral components which can induce innate immune responses in human peripheral blood mononuclear cells (PBMC), we investigated the anti-neoplastic agent Newcastle disease virus (NDV) and its two spike proteins hemagglutinin-neuraminidase (HN) and fusion protein (F). NDV was an excellent inducer in PBMC of IFN-alpha production and capable of inducing upregulation of plasma membrane expression of tumor necrosis factor related apoptosis inducing ligand (TRAIL). Viral replication was not required for these responses because NDV inactivated for 5 min by UV was as good as live NDV. NDV-modified and paraformaldehyde-fixed BHK cells could also trigger IFN-alpha and TRAIL induction, indicating that contacts of responder cells with NDV-modified cell surfaces are sufficient to induce these activities in PBMC. Antibodies against HN but not F were able to block these responses. Finally we could show that HN but not F induced IFN-alpha and TRAIL in PBMC. This was possible through the use of respective gene transfectants generated with the help of Semliki Forest virus (SFV) replicase-based DNA recombinant expression systems. Upon contact with BHK cells expressing HN but not F at their cell surface, human PBMC produced IFN-alpha and some cells, including monocytes and T lymphocytes, upregulated cell surface TRAIL expression.