Activation of the Apoptotic Fas Antigen-Encoding Gene Upon Influenza Virus Infection Involving Spontaneously Produced Beta-Interferon

Virology. 1995 Jun 1;209(2):288-96. doi: 10.1006/viro.1995.1260.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminopurine / pharmacology
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Surface / biosynthesis*
  • Antigens, Surface / genetics
  • Apoptosis / genetics*
  • Base Sequence
  • Blotting, Northern
  • Cell Line
  • Cycloheximide / pharmacology
  • DNA Primers
  • Flow Cytometry
  • Gene Expression Regulation* / drug effects
  • HeLa Cells
  • Humans
  • Influenza A virus / physiology*
  • Interferon-beta / biosynthesis*
  • Interferon-beta / immunology
  • Interferon-beta / pharmacology
  • Kinetics
  • Molecular Sequence Data
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Poly I-C / pharmacology
  • Polymerase Chain Reaction
  • Protein Kinases / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • fas Receptor

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, Surface
  • DNA Primers
  • Phosphoproteins
  • RNA, Messenger
  • fas Receptor
  • 2-Aminopurine
  • Interferon-beta
  • Cycloheximide
  • Protein Kinases
  • Poly I-C