Effect of N‑terminal region of human parvovirus B19‑VP1 unique region on cardiac injury in naïve mice

The viral protein 1 unique region (VP1u) of human parvovirus B19 (B19V) is a multifunctional capsid protein with essential roles in virus tropism, uptake, and subcellular trafficking. These functions reside on hidden protein domains, which become accessible upon interaction with cell membrane receptors. A receptor-binding domain (RBD) in VP1u is responsible for the specific targeting and uptake of the virus exclusively into cells of the erythroid lineage in the bone marrow. A phospholipase A2 domain promotes the endosomal escape of the incoming virus. The VP1u is also the immunodominant region of the capsid as it is the target of neutralizing antibodies. For all these reasons, the VP1u has raised great interest in antiviral research and vaccinology. Besides the essential functions in B19V infection, the remarkable erythroid specificity of the VP1u makes it a unique erythroid cell surface biomarker. Moreover, the demonstrated capacity of the VP1u to deliver diverse cargo specifically to cells around the proerythroblast differentiation stage, including erythroleukemic cells, offers novel therapeutic opportunities for erythroid-specific drug delivery. In this review, we focus on the multifunctional role of the VP1u in B19V infection and explore its potential in diagnostics and erythroid-specific therapeutics.

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Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface.

Journal of Clinical Investigation ◽

10.1172/jci115812 ◽

1992 ◽

Vol 89 (6) ◽

pp. 2023-2029 ◽

Cited By ~ 68

Author(s):

S J Rosenfeld ◽

K Yoshimoto ◽

S Kajigaya ◽

S Anderson ◽

N S Young ◽

...

Keyword(s):

Capsid Protein ◽

Parvovirus B19 ◽

Human Parvovirus B19 ◽

Unique Region ◽

Minor Capsid Protein ◽

Virion Surface

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Up-regulation of adhesion molecule expression and induction of TNF-α on vascular endothelial cells by antibody against human parvovirus B19 VP1 unique region protein

Clinica Chimica Acta ◽

10.1016/j.cca.2008.05.012 ◽

2008 ◽

Vol 395 (1-2) ◽

pp. 77-83 ◽

Cited By ~ 12

Author(s):

Bor-Show Tzang ◽

Chun-Chou Tsai ◽

Chun-Ching Chiu ◽

Jing-Yu Shi ◽

Tsai-Ching Hsu

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Vascular Endothelial Cells ◽

Parvovirus B19 ◽

Vascular Endothelial ◽

Adhesion Molecule Expression ◽

Human Parvovirus B19 ◽

Unique Region ◽

Tnf Α

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Phospholipase A2 Activity-Dependent Stimulation of Ca2+ Entry by Human Parvovirus B19 Capsid Protein VP1

Journal of Virology ◽

10.1128/jvi.01041-06 ◽

2006 ◽

Vol 80 (22) ◽

pp. 11370-11380 ◽

Cited By ~ 40

Author(s):

Adrian Lupescu ◽

C.-Thomas Bock ◽

Philipp A. Lang ◽

Susanne Aberle ◽

Heike Kaiser ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Phospholipase A2 ◽

Capsid Protein ◽

Parvovirus B19 ◽

Eukaryotic Expression ◽

Expression Vectors ◽

Human Parvovirus B19 ◽

Pla2 Activity ◽

Unique Region ◽

The Impact

ABSTRACT Recent reports demonstrated an association of human parvovirus B19 with inflammatory cardiomyopathy (iCMP), which is accompanied by endothelial dysfunction. As intracellular Ca2+ activity is a key regulator of cell function and participates in mechanisms leading to endothelial dysfunction, the present experiments explored the effects of the B19 capsid proteins VP1 and VP2. A secreted phospholipase A2 (PLA2)-like activity has been located in the VP1 unique region of the B19 minor capsid protein. As PLA2 has recently been shown to activate the store-operated or capacitative Ca2+ channel ICRAC, we analyzed the impact of the viral PLA2 motif on Ca2+ entry. We cloned the VP1 and VP2 genes isolated from a patient suffering from fatal B19 iCMP into eukaryotic expression vectors. We also generated a B19 replication-competent plasmid to demonstrate PLA2 activity under the control of the complete B19 genome. After the transfection of human endothelial cells (HMEC-1), cytosolic Ca2+ activity was determined by utilizing Fura-2 fluorescence. VP1 and VP2 expression did not significantly modify basal cytosolic Ca2+ activity or the decline of cytosolic Ca2+ activity following the removal of extracellular Ca2+. However, expression of VP1 and of the full-length B19 clone, but not of VP2, significantly accelerated the increase of cytosolic Ca2+ activity following the readdition of extracellular Ca2+ in the presence of thapsigargin, indicating an activation of ICRAC. The effect of VP1 was mimicked by the PLA2 product lysophosphatidylcholine and abolished by an inactivating mutation of the PLA2-encoding region of the VP1 gene. Our observations point to the activation of Ca2+ entry by VP1 PLA2 activity, an effect likely participating in the pathophysiology of B19 infection.

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