Down-Regulation of Inwardly Rectifying Kir2.1 K+ Channels by Human Parvovirus B19 Capsid Protein VP1

作者：Ahmed Musaab; Elvira Bernat; Almilaji Ahmad; Bock C Thomas; Kandolf Reinhard; Lang Florian^*

来源：Journal of Membrane Biology, 2015, 248(2): 223-229.

DOI：10.1007/s00232-014-9762-9

• Parvovirus B19
• Phospholipase A2
• Channels
• Xenopus
• ATPase

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 mu g/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.

• 出版日期2015-4