Enhancement of phospholipase activity during poliovirus infection.
Infection of human cells with poliovirus leads to modification of phospholipase activity. Phospholipase C, which generates inositol triphosphate, is stimulated, whereas the activation of phospholipase A2 by the calcium ionophore A23187 is inhibited. Analysis of phospholipid moieties in media of HeLa cells infected with poliovirus indicates that the release of fatty acids is not enhanced during infection, suggesting that phospholipase A1 and A2 activities are not stimulated. The release of choline into the medium is significantly higher 3 h after infection, indicating that a phospholipase that has phosphatidylcholine as its substrate becomes activated. This activation requires viral gene expression because inhibitors of poliovirus gene expression added at the beginning of infection block choline release, but continuous viral protein synthesis is not required. Choline and phosphorylcholine are released into the medium, but the pools of both are gradually depleted in poliovirus-infected cells, perhaps as a consequence of their release into the medium and the increased synthesis of phospholipids that takes place in poliovirus-infected cells. Inhibitors of phospholipase activity such as mepacrine, zinc or cadmium ions significantly reduce this increased release of choline from poliovirus-infected cells. Labelling of cells with [3H]phosphatidylcholine suggests that the choline released from infected cells comes, at least in part, from the hydrolysis of this compound. These results indicate that, in addition to the activation of the phospholipase C which hydrolyses phosphatidylinositol in poliovirus-infected cells, a phospholipase C that acts on a phosphatidylcholine is also activated.
Centro de Biologia Molecular, UAM-CSIC, Madrid, Spain.
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Irurzun
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Pérez
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Carrasco
D002104:Cadmium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002794:Choline / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010767:Phosphorylcholine / Q000378:metabolism; D017955:Poliovirus / Q000254:growth & development*; D011796:Quinacrine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
D010716:Phosphatidylinositols; D002104:Cadmium; D010767:Phosphorylcholine; D010740:Phospholipases; D010738:Type C Phospholipases; D011796:Quinacrine; D015032:Zinc; D002794:Choline