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Phospholipase A2-Activity Dependent Stimulation of Ca2+ Entry by Human Parvovirus B19 Capsid Protein VP1

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Lupescu A, Bock CT, Lang PA, Aberle S, Kaiser H, Kandolf R, Lang F.

Editorial: Journal of Virology, 2006.

Rezumat:

Recent reports demonstrated an association of human parvovirus B19 (B19) with inflammatory cardiomyopathy (iCMP) which is accompanied by endothelial dysfunction. As intracellular Ca2+-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 on the regulation of cytosolic Ca2+-activity. A secreted phospholipase A2 (PLA2)-like activity has recently been located in the VP1-unique region of the B19 minor capsid protein. Here, we analyzed the impact of the viral PLA2-motif on the cytosolic Ca2+-activity. We cloned the VP1- and VP2-gene isolated from a patient suffering from fatal B19-iCMP into eukaryotic expression vectors. We exerted a B19-infectious clone to demonstrate the PLA2-activity under the control of the complete B19-genome. Additionally, a VP1 PLA2-negative mutant was constructed. After transfection of human endothelial cells (HMEC-1) cytosolic Ca2+-activity was determined utilizing Fura-2 fluorescence. VP1 and VP2 expression did not significantly modify basal cytosolic Ca2+-activity nor the decline of cytosolic Ca2+-activity following removal of extracellular Ca2+. However, expression of VP1 and of the full-length B19-clone, but not of VP2, significantly accelerated the increase of cytosolic Ca2+-activity following readdition of extracellular Ca2+ in the presence of thapsigargin, indicating an activation of store operated or capacitative Ca2+-channel ICRAC. The effect of VP1 was mimicked by the PLA2 product lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2 encoding region of VP1. Our observations point to the activation of Ca2+-entry by the VP1 PLA2-activity, an effect likely participating in the pathophysiology of B19-infection.

Cuvinte cheie: Viral myocarditis, phospholipase A2, capacitative Ca2+ channel ICRAC, cytosolic Ca2+-activity

URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16956939&query_hl=1&itool=pubmed_docsum