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

Abstract

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 ^H153AVP1 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 ^H153AVP1. The effect of VP1 on I _K was mimicked by lysophosphatidylcholine (1 μg/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.