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

Cellular Physiology and Biochemistry

关键词: 4-bromophenacylbromide;    Na+/K+ ATPase;    Lysophosphatidylcholine;    Viral myocarditis;    VP1;    Phospholipase A2;   

DOI  :  10.1159/000350083

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND