Augmentation of verotoxin-induced cytotoxicity/apoptosis by interferon is repressed in cells persistently infected with mumps virus.

Verotoxin type 2 (VT2) produced by enterohemorrhagic Escherichia coli (EHEC) has been shown to have high cytotoxic potency toward several human B lymphoid cell lines with and without Epstein-Barr virus (EBV), Cell death, apoptosis induced by VT2, is closely correlated with the expression of receptor molecule Gb3/CD77, recognized by the toxin, but not with the infection or presence of EBV, Pretreatment of cells with interferon-alpha (IFN-alpha) for 24 h resulted in augmentation of apoptosis by VT2, Pretreatment within 8 h, however, was not effective, It has been reported that IFN-alpha-induced apoptosis is correlated with the induction of the 2',5'-OAS/RNase L system or dsRNA-activated protein kinase (PKR) or both. We have established persistent infection in both Akata and P3HR-1 cells with mumps virus. The persistently infected cell lines, P3HR-MP2 and Akata-MP2, showed poor induction of 2',5'-OAS and PKR in response to IFN-alpha. Augmentation of VT2-induced apoptosis by IFN-alpha was not found in the cell lines P3HR-MP2 and Akata-MP2, Therefore, these findings were interpreted to indicate that augmentation of VT2-induced apoptosis by IFN-alpha may be mediated by PKR and the 2',5'-OAS/RNaseL system, It is also suggested that mumps virus can suppress apoptosis and establish persistent infection.