Down-Regulation of Na+/K+ ATPase Activity by Human Parvovirus B19 Capsid Protein VP1

作者：Almilaji Ahmad; Szteyn Kalina; Fein Evelyn; Pakladok Tatsiana; Munoz Carlos; Elvira Bernat; Towhid Syeda T; Alesutan Ioana; Shumilina Ekaterina; Bock C Thomas; Kandolf Reinhard; Lang Florian^*

来源：Cellular Physiology and Biochemistry, 2013, 31(4-5): 638-648.

DOI：10.1159/000350083

• Viral myocarditis
• VP1
• Phospholipase A2
• Na+/K+ ATPase
• Lysophosphatidylcholine
• 4-bromophenacylbromide

Background/Aims: 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 mu M for 36 hours) but was abrogated in the presence of PLA2 specific blocker 4-bromophenacylbromide (50 mu M) and was mimicked by lysophosphatidylcholine (0.5 - 1 mu g/ml). According to whole cell patch clamp, lysophosphatidylcholine (1 mu g /ml) similarly decreased I-pump in human microvascular endothelial cells (HMEC). Conclusion: 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.

• 出版日期2013