Phospholipase C and phospholipase A2 are involved in the antiviral activity of human interferon-alpha.
Treatment of human amniotic cells (UAC) with human interferon-alpha (Hu-IFN alpha) or phorbol myristate acetate (PMA) resulted in translocation of protein kinase C (PK-C) activity from the cytosol fraction to that of the membranes. Analysis of 32P incorporation into phospholipid fractions and studies of alterations in fatty acid content for the major phospholipids of IFN-treated cells suggest that phospholipases C and A2 are activated by Hu-IFN alpha. Addition of neomycin (an inhibitor of phospholipase C), as well as mepacrine (an inhibitor of phospholipase A2) to IFN-treated cells inhibited the antiviral activity of Hu-IFN alpha in the vesicular stomatitis virus (VSV)-UAC system used. These observations indicate that (i) activation of PK-C and (ii) diacylglycerol formation, arachidonic acid and/or lysophosphatidylcholine release are important steps in the mechanism of action of IFN.
Premecz
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Microbiological Research Group, National Institute of Hygiene, Budapest, Hungary.
Markovits
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A
Bagi
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Farkas
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T
Földes
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I
D000650:Amnion / Q000166:cytology / Q000201:enzymology; D000998:Antiviral Agents; D002478:Cells, Cultured; D004789:Enzyme Activation; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009355:Neomycin / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication
D000998:Antiviral Agents; D005227:Fatty Acids; D007370:Interferon Type I; D010743:Phospholipids; D011493:Protein Kinase C; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011796:Quinacrine; D009355:Neomycin