title: Down-regulation of K⁺ channels by human parvovirus B19 capsid protein VP1.
abstract: Parvovirus B19 (B19V) can cause inflammatory cardiomyopathy and endothelial dysfunction. Pathophysiological mechanisms involved include lysophosphatidylcholine producing phospholipase A2 (PLA2) activity of the B19V capsid protein VP1. Most recently, VP1 and lysophosphatidylcholine have been shown to inhibit Na(+)/K(+) ATPase. The present study explored whether VP1 modifies the activity of Kv1.3 and Kv1.5 K(+) channels. cRNA encoding Kv1.3 or Kv1.5 was injected into Xenopus oocytes without or with cRNA encoding VP1 isolated from a patient suffering from fatal B19V-induced myocarditis. K(+) channel activity was determined by dual electrode voltage clamp. Injection of cRNA encoding Kv1.3 or Kv1.5 into Xenopus oocytes was followed by appearance of Kv K(+) channel activity, which was significantly decreased by additional injection of cRNA encoding VP1, but not by additional injection of cRNA encoding PLA2-negative VP1 mutant (H153A). The effect of VP1 on Kv current was not significantly modified by transcription inhibitor actinomycin (10 μM for 36 h) but was mimicked by lysophosphatidylcholine (1 μg/ml). The B19V capsid protein VP1 inhibits host cell Kv channels, an effect at least partially due to phospholipase A2 (PLA) dependent formation of lysophosphatidylcholine.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Musaab
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.affiliation: Department of Molecular Pathology, University of Tübingen, Germany.
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.affiliation: Department of Molecular Pathology, University of Tübingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.affiliation: Department of Physiology, University of Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D016732:Parvovirus B19, Human / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D014981:Xenopus
chemical_list: D036022:Capsid Proteins; D015221:Potassium Channels; C095547:capsid protein VP1, parvovirus B19
keywords: K(+) channels; Kv1.3; Kv1.5; Lysophosphatidylcholine; Phospholipase A2; Viral myocarditis