title: Down-regulation of Na/K+ atpase activity by human parvovirus B19 capsid protein VP1.
abstract: OBJECTIVE
  Human parvovirus B19 (B19V) may cause inflammatory cardiomyopathy (iCMP) which is accompanied by endothelial dysfunction. The B19V capsid protein VP1 contains a lysophosphatidylcholine producing phospholipase A2 (PLA) sequence. Lysophosphatidylcholine has in turn been shown to inhibit Na(+)/K(+) ATPase. The present study explored whether VP1 modifies Na(+)/K(+) ATPase activity.
  
  
  METHODS
  Xenopus oocytes were injected with cRNA encoding VP1 isolated from a patient suffering from fatal B19V-iCMP or cRNA encoding PLA2-negative VP1 mutant (H153A) and K(+) induced pump current (I(pump)) as well as ouabain-inhibited current (I(ouabain)) both reflecting Na(+)/K(+)-ATPase activity were determined by dual electrode voltage clamp.
  
  
  RESULTS
  Injection of cRNA encoding VP1, but not of VP1(H153A) or water, was followed by a significant decrease of both, I(pump) and I(ouabain) in Xenopus oocytes. The effect was not modified by inhibition of transcription with actinomycin (10 µM for 36 hours) but was abrogated in the presence of PLA2 specific blocker 4-bromophenacylbromide (50 µM) and was mimicked by lysophosphatidylcholine (0.5 - 1 µg/ml). According to whole cell patch clamp, lysophosphatidylcholine (1 µg /ml) similarly decreased I(pump) in human microvascular endothelial cells (HMEC).
  
  
  CONCLUSIONS
  The B19V capsid protein VP1 is a powerful inhibitor of host cell Na(+)/K(+) ATPase, an effect at least partially due to phospholipase A2 (PLA2) dependent formation of lysophosphatidylcholine.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: Kalina
authors.initials: K
authors.lastname: Szteyn
authors.forename: Evelyn
authors.initials: E
authors.lastname: Fein
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Pakladok
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Bernat
authors.initials: B
authors.lastname: Elvira
authors.forename: Syeda T
authors.initials: ST
authors.lastname: Towhid
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
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: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D016732:Parvovirus B19, Human / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development
chemical_list: D000098:Acetophenones; D036022:Capsid Proteins; D008244:Lysophosphatidylcholines; C095547:capsid protein VP1, parvovirus B19; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase; C006821:4-bromophenacyl bromide