title: Down-regulation of inwardly rectifying Kir2.1 K+ channels by human parvovirus B19 capsid protein VP1.
abstract: Parvovirus B19 (B19V) has previously been shown to cause endothelial dysfunction. B19V capsid protein VP1 harbors a lysophosphatidylcholine producing phospholipase A2 (PLA2). Lysophosphatidylcholine inhibits Na(+)/K(+) ATPase, which in turn may impact on the activity of inwardly rectifying K(+) channels. The present study explored whether VP1 modifies the activity of Kir2.1 K(+) channels. cRNA encoding Kir2.1 was injected into Xenopus oocytes without or with cRNA encoding VP1 isolated from a patient suffering from fatal B19V-induced inflammatory cardiomyopathy or the VP1 mutant (H153A)VP1 lacking a functional PLA2 activity. K(+) channel activity was determined by dual electrode voltage clamp. In addition, Na(+)/K(+)-ATPase activity was estimated from K(+)-induced pump current (I(pump)) and ouabain-inhibited current (I(ouabain)). Injection of cRNA encoding Kir2.1 into Xenopus oocytes was followed by appearance of inwardly rectifying K(+) channel activity (I(K)), which was significantly decreased by additional injection of cRNA encoding VP1, but not by additional injection of cRNA encoding (H153A)VP1. The effect of VP1 on I K was mimicked by lysophosphatidylcholine (1 μg/ml) and by inhibition of Na(+)/K(+)-ATPase with 0.1 mM ouabain. In the presence of lysophosphatidylcholine, I K was not further decreased by additional treatment with ouabain. The B19V capsid protein VP1 thus inhibits Kir2.1 channels, an effect at least partially due to PLA2-dependent formation of lysophosphatidylcholine with subsequent inhibition of Na(+)/K(+)-ATPase activity.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Musaab
authors.initials: M
authors.lastname: Ahmed
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials; D009865:Oocytes / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
chemical_list: D036022:Capsid Proteins; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; C095547:capsid protein VP1, parvovirus B19