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10.1128/JVI.01041-06

http://scihub22266oqcxt.onion/10.1128/JVI.01041-06
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16956939!1642163!16956939
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suck abstract from ncbi


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pmid16956939      J+Virol 2006 ; 80 (22): 11370-80
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  • Phospholipase A2 activity-dependent stimulation of Ca2+ entry by human parvovirus B19 capsid protein VP1 #MMPMID16956939
  • Lupescu A; Bock CT; Lang PA; Aberle S; Kaiser H; Kandolf R; Lang F
  • J Virol 2006[Nov]; 80 (22): 11370-80 PMID16956939show ga
  • Recent reports demonstrated an association of human parvovirus B19 with inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial dysfunction. As intracellular Ca(2+) activity is a key regulator of cell function and participates in mechanisms leading to endothelial dysfunction, the present experiments explored the effects of the B19 capsid proteins VP1 and VP2. A secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique region of the B19 minor capsid protein. As PLA2 has recently been shown to activate the store-operated or capacitative Ca(2+) channel I(CRAC), we analyzed the impact of the viral PLA2 motif on Ca(2+) entry. We cloned the VP1 and VP2 genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic expression vectors. We also generated a B19 replication-competent plasmid to demonstrate PLA2 activity under the control of the complete B19 genome. After the transfection of human endothelial cells (HMEC-1), cytosolic Ca(2+) activity was determined by utilizing Fura-2 fluorescence. VP1 and VP2 expression did not significantly modify basal cytosolic Ca(2+) activity or the decline of cytosolic Ca(2+) activity following the removal of extracellular Ca(2+). However, expression of VP1 and of the full-length B19 clone, but not of VP2, significantly accelerated the increase of cytosolic Ca(2+) activity following the readdition of extracellular Ca(2+) in the presence of thapsigargin, indicating an activation of I(CRAC.) The effect of VP1 was mimicked by the PLA2 product lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2-encoding region of the VP1 gene. Our observations point to the activation of Ca(2+) entry by VP1 PLA2 activity, an effect likely participating in the pathophysiology of B19 infection.
  • |Calcium/*metabolism[MESH]
  • |Capsid Proteins/genetics/*physiology[MESH]
  • |Cell Line[MESH]
  • |Cell Line, Tumor[MESH]
  • |Cytoplasm/chemistry[MESH]
  • |Endothelial Cells/virology[MESH]
  • |Fluorescence[MESH]
  • |Fura-2/metabolism[MESH]
  • |Humans[MESH]
  • |Parvovirus B19, Human/genetics/*physiology[MESH]
  • |Phospholipases A/genetics/*metabolism[MESH]
  • |Phospholipases A2[MESH]
  • |Staining and Labeling[MESH]


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