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.
Hariya
Y
Y
Department of Oral Surgery, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Shirakawa
S
S
Yonekura
N
N
Yokosawa
N
N
Kohama
G I
GI
Fujii
N
N
D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002908:Chronic Disease; D003603:Cytotoxins / Q000633:toxicity*; D004357:Drug Synergism; D004926:Escherichia coli; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D009107:Mumps / Q000188:drug therapy*; D009109:Mumps virus; D022641:Shiga Toxin 2; D015398:Signal Transduction / Q000187:drug effects
D000998:Antiviral Agents; D001427:Bacterial Toxins; D003603:Cytotoxins; D016898:Interferon-alpha; D022641:Shiga Toxin 2