ACTIVATION OF THE APOPTOTIC FAS ANTIGEN-ENCODING GENE UPON INFLUENZA-VIRUS INFECTION INVOLVING SPONTANEOUSLY PRODUCED INTERFERON-BETA

We previously demonstrated that influenza virus infection induces apop tosis in culture cells. Here, we examined the activation of the Fas an tigen gene that encodes an apoptosis-mediating membrane protein in the virus-infected cells. The virus elicited a transient but marked incre ase in Pas antigen mRNA 3 to 4 hr after infection, followed by the exp ression of the antigen on the cell surface. Poly(l)-poly(C), a synthet ic double-stranded RNA, similarly activated Pas antigen gene expressio n, and poly(l)-poly(C)-treated cells are highly susceptible to the cel l killing effect of lgM isotype of anti-Pas monoclonal antibody. On th e other hand, the IgG isotype of anti-Pas monoclonal antibody, which h as an inhibitory effect on Fas Ag-mediated cell death, suppressed the virus-induced cell death. Prior exposure of the cells to anti-interfer on-beta antibody decreased the degree of cell death as well as the amo unt of Pas mRNA The autophosphorylation activity of double-stranded RN A-activated protein kinase was also decreased in the antibody-treated cells. Moreover, a protein kinase inhibitor, 2-aminopurine, blocked th e Pas Ag gene activation by poly(l)-poly(C). These results suggested t hat the activation of Pas Ag gene in the early phase of infection is a n important event for apoptosis, and that it is regulated by the doubl e-stranded RNA/interferon system involving protein phosphorylation. (C ) 1995 Academic Press, Inc.