Down-regulation of Na/K + ATPase activity by human parvovirus B19 capsid protein VP1

Abstract

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 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). 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. © 2013 S. Karger AG, Basel.