Mumps virus can suppress the effective augmentation of HPC-induced apoptosis by IFN-gamma through disruption of IFN signaling in U937 cells.

Abstract

Cells of the human promonocytic cell line U937 were found to be sensitive to hexadecylphosphocholine (HPC), which is a potential anticancer drug. Induction of apoptosis was found in U937 cells after treatment with HPC for 24 to 48 hr. The apoptosis in U937 cells exposed to HPC was increased significantly in the presence of interferon-gamma (IFN-gamma). The augmentation of HPC-induced apoptosis by IFN-gamma is repressed in cells (U937-MP) persistently infected with mumps virus. A persistently infected cell line, U937-MP, showed poor induction of signal transducers and activators of transcription-1alpha (STAT-alpha), STAT-2, p48 and IFN-regulatory factor-1 (IRF-1), which are closely correlated with interferon-alpha (IFN-alpha) and IFN-gamma signaling pathways. Expression of MHC class-I or class-II was augmented by IFN-alpha or IFN-gamma in U937 cells, but not in persistently infected cells. Therefore, it is suggested that the IFN-gamma signaling pathway plays an important role in the augmentation of HPC-induced apoptosis. Mumps virus can suppress the IFN-gamma signaling pathway and subsequent development of apoptosis.