Down-regulation of inwardly rectifying Kir2.1 K+ channels by human parvovirus B19 capsid protein VP1.

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 (Ipump) and ouabain-inhibited current (Iouabain). Injection of cRNA encoding Kir2.1 into Xenopus oocytes was followed by appearance of inwardly rectifying K+ channel activity (IK), 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 IK was mimicked by lysophosphatidylcholine (1 μg/ml) and by inhibition of Na+/K+-ATPase with 0.1 mM ouabain. In the presence of lysophosphatidylcholine, IK 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.