Effects of antibodies against human parvovirus B19 on angiogenic signaling.

Abstract

Human parvovirus B19 (B19V) infection has symptoms similar to those of anti‑phospholipid syndrome(APS). Antibodies against B19V‑VP1 unique region(VP1u) exhibit activity similar to that of anti‑phospholipid antibodies(aPLs) by inducing vascular endothelial cell adhesion factors and APS‑like syndrome. Previous studies have identified an effect of aPLs on angiogenesis. However, little is understood regarding the effect of anti‑B19V‑VP1u antibodies on angiogenesis. The present study investigated the effects of anti‑B19V‑VP1u antibodies on the expression of adhesion molecules and angiogenic signaling using an aPL‑induced human umbilical vein endothelial cell(HUVEC) model, and trypan blue staining and western blotting. The effect of B19V‑VP1u antibodies on vascular endothelial growth factor(VEGF) expression in A549 cells, another well‑known model used to study angiogenesis, was also examined. Significantly higher intracellular adhesion molecule1 expression was observed following treatments with 10%fetal calf serum (FCS), aPL immunoglobulinG (IgG), B19V‑VP1u IgG or B19V‑NS1 IgG, compared with in the normal human (NH) IgG‑treated cells. Conversely, significantly higher vascular cellular adhesion molecule1 was only detected in HUVECs treated with B19V‑VP1u IgG. Significantly increased integrinβ1 was detected in HUVECs treated with aPLIgG or B19V‑VP1u IgG, whereas no difference in integrinβ1 was observed in those treated with 10%FCS, NH IgG or B19V‑NS1 IgG. No difference in AKT‑mTOR‑S6 ribosomal protein (S6RP) signaling was observed in HUVECs treated with B19‑VP1u IgG or B19V‑NS1 IgG, compared with NH IgG‑treated cells. Significantly higher human inducible factor‑1α was detected in HUVECs treated with 10%FCS, aPLIgG, B19V‑VP1u IgG or B19V‑NS1 IgG, compared with in NH IgG‑treated cells. However, there was no difference in the level of VEGF observed among HUVECs treated with NH IgG, B19V‑VP1u IgG or B19V‑NS1 IgG. Notably, no difference in VEGF level was observed in A549 cells treated with NH IgG, aPLIgG, B19V‑VP1u IgG or B19V‑NS1 IgG. These findings suggest that anti‑B19V‑VP1u antibodies may serve a role in activating adhesion molecules, but not in AKT‑mTOR‑S6RP signaling.