title: Up-regulation of epithelial Na(+) channel ENaC by human parvovirus B19 capsid protein VP1.
abstract: BACKGROUND
  Clinical disorders caused by parvovirus B19 (B19V) infection include endothelial dysfunction with cardiac ischemia. The virus is effective in part by lysophosphatidylcholine-producing phospholipase A2 (PLA2) activity of B19V capsid protein VP1. Mechanisms compromising endothelial function include up-regulation of amiloride sensitive epithelial Na(+)-channel ENaC leading to endothelial cell stiffness. Regulators of ENaC include ubiquitin-ligase Nedd4-2. The present study explored whether VP1 modifies ENaC-activity.
  
  
  METHODS
  cRNA encoding ENaC was injected into Xenopus oocytes without or with cRNA encoding VP1. Experiments were made with or without coexpression of Nedd4-2. ENaC activity was estimated from amiloride (50 μM) sensitive current.
  
  
  RESULTS
  Injection of cRNA encoding ENaC into Xenopus oocytes was followed by appearance of amiloride sensitive current, which was significantly enhanced 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 ENaC was mimicked by treatment of ENaC expressing oocytes with lysophosphatidylcholine (1 μg/ml). The effect of VP1 and lysophosphatidylcholine was not additive. ENaC activity was downregulated by Nedd4-2, an effect not reversed by VP1.
  
  
  CONCLUSIONS
  The B19V capsid protein VP1 up-regulates ENaC, an effect at least partially due to phospholipase A2 (PLA) dependent formation of lysophosphatidylcholine.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Musaab
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Lisann
authors.initials: L
authors.lastname: Pelzl
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fezai
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.affiliation: Department of Molecular Pathology, University of Tuebingen, Liebermeisterstraße 8, 72076 Tuebingen, Germany.
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.affiliation: Department of Molecular Pathology, University of Tuebingen, Liebermeisterstraße 8, 72076 Tuebingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D000075702:Nedd4 Ubiquitin Protein Ligases; D009865:Oocytes / Q000821:virology; D010322:Parvoviridae Infections / Q000378:metabolism* / Q000821:virology; D016732:Parvovirus B19, Human / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D036022:Capsid Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D008244:Lysophosphatidylcholines; D029867:Xenopus Proteins; C095547:capsid protein VP1, parvovirus B19; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618482:Nedd4 protein, Xenopus; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C000618460:nedd4l protein, Xenopus; D044767:Ubiquitin-Protein Ligases
keywords: Lysophosphatidylcholine; Nedd4-2; Oocyte; PVB19; Phospholipase A2; Viral myocarditis