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Cell-membrane phospholipase C is involved in inducing the antiviral effect of interferon

L M Popescu1, C Cernescu, I I Moraru

  • 1Division of Cell Biology, Faculty of Medicine, Bucharest, Romania.

Bioscience Reports
|October 1, 1989
PubMed

Insights

Human interferons alpha and beta trigger antiviral effects through phosphoinositide hydrolysis. Inhibiting phospholipase C blocked this antiviral action, indicating its crucial role in interferon signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Human interferons (IFNs) alpha and beta are key cytokines mediating antiviral responses.
  • The precise intracellular signaling mechanisms by which IFNs exert their antiviral effects are not fully elucidated.
  • Phospholipase C (PLC) is an enzyme involved in signal transduction pathways.

Purpose of the Study:

  • To investigate the role of phospholipase C (PLC) and its products in mediating the antiviral effects of human interferons alpha and beta.
  • To determine if phosphoinositide hydrolysis is a critical step in interferon-induced antiviral activity.

Main Methods:

  • Utilized a monospecific inhibitory antibody against phospholipase C (PLC) to block its activity in human fibroblasts and Vero cells challenged with vesicular stomatitis virus (VSV).
  • Assessed the antiviral effect of interferons (IFNs) alpha and beta in the presence and absence of PLC inhibition.
  • Employed F(ab')2 fragments of the antibody to confirm specificity.
  • Used liposomes containing specific phosphoinositide second messengers to protect cells.

Main Results:

  • A monospecific antibody inhibiting phospholipase C (PLC) blocked the antiviral effects of human interferons alpha and beta against vesicular stomatitis virus.
  • This inhibition was specific to PLC, as antibodies against phospholipase A2 and other PLC types had no effect.
  • Exogenous administration of phosphoinositide-derived second messengers (inositol 1,4,5-triphosphate and 1-oleoyl-2-acetyl-rac-glycerol) conferred antiviral protection, independent of interferon induction.

Conclusions:

  • Phosphoinositide-derived second messengers are critically involved in triggering the antiviral effects of human interferons alpha and beta.
  • Specific inhibition of phospholipase C (PLC) activity abrogates the antiviral state induced by interferons.
  • These findings elucidate a key intracellular signaling pathway for interferon antiviral activity.

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