title: Activation of the apoptotic Fas antigen-encoding gene upon influenza virus infection involving spontaneously produced beta-interferon.
abstract: We previously demonstrated that influenza virus infection induces apoptosis in culture cells. Here, we examined the activation of the Fas antigen gene that encodes an apoptosis-mediating membrane protein in the virus-infected cells. The virus elicited a transient but marked increase in Fas antigen mRNA 3 to 4 hr after infection, followed by the expression of the antigen on the cell surface. Poly(I)-poly(C), a synthetic double-stranded RNA, similarly activated Fas antigen gene expression, and poly(I)-poly(C)-treated cells are highly susceptible to the cell killing effect of IgM isotype of anti-Fas monoclonal antibody. On the other hand, the IgG isotype of anti-Fas monoclonal antibody, which has an inhibitory effect on Fas Ag-mediated cell death, suppressed the virus-induced cell death. Prior exposure of the cells to anti-interferon-beta antibody decreased the degree of cell death as well as the amount of Fas mRNA. The autophosphorylation activity of double-stranded RNA-activated protein kinase was also decreased in the antibody-treated cells. Moreover, a protein kinase inhibitor, 2-aminopurine, blocked the Fas Ag gene activation by poly(I)-poly(C). These results suggested that the activation of Fas Ag gene in the early phase of infection is an important event for apoptosis, and that it is regulated by the double-stranded RNA/interferon system involving protein phosphorylation.
authors.affiliation: Department of Biochemistry, Aichi Human Service Center, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takizawa
authors.forename: R
authors.initials: R
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D015075:2-Aminopurine / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D016899:Interferon-beta / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D019014:fas Receptor
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D017931:DNA Primers; D010750:Phosphoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D015075:2-Aminopurine; D016899:Interferon-beta; D003513:Cycloheximide; D011494:Protein Kinases; D011070:Poly I-C