Effects of antibodies against human parvovirus B19 on angiogenic signaling

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 molecule 1 expression was observed following treatments with 10% fetal calf serum (FCS), aPL immunoglobulin G (IgG), B19V-VP1u IgG or B19V-NS1 IgG, compared with in the normal human (NH) IgG-treated cells. Conversely, significantly higher vascular cellular adhesion molecule 1 was only detected in HUVECs treated with B19V-VP1u IgG. Significantly increased integrin β1 was detected in HUVECs treated with aPL IgG or B19V-VP1u IgG, whereas no difference in integrin β1 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, aPL IgG, 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, aPL IgG, 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.