Abstract
Foot-and-mouth disease virus (FMDV) binds to cellular integrins through an RGD motif in its capsid protein, VP1. It is unclear, however, what kind of cellular event(s) are triggered after the binding of VP1 to the cells. In this study, we show that aqueous soluble recombinant DNA-derived VP1 (rVP1) of FMDV induced apoptosis of BHK-21 cells after binding to integrins. In addition, treatment of BHK-21 cells with rVP1 resulted in deactivation of Akt and enhancement of several proapoptotic responses such as dephosphorylation of glycogen synthase kinase-3beta and cleavage of procaspase-3, -7, and -9. Additional studies revealed that the rVP1 treatment caused apoptosis of cancer cells, including MCF-7 (a breast carcinoma cell line with a functional deletion of the caspase-3 gene) and PC-3 (a sphingosine 1-phosphate receptor subtype 3-deficient androgen-independent prostate cancer cell line). These results suggest that rVP1 of FMDV may be used selectively as a potent apoptotic agent for human cancer by modulating the Akt signaling pathway and that its effect is not primarily dependent on either activation of procaspase-3 or deactivation of sphingosine 1-phosphate receptor subtype 3.
Highlights
Foot-and-mouth disease virus (FMDV)1 is the etiological agent of foot-and-mouth disease, a deadly epidemic that affects many economically important domestic livestock such as cattle, pigs, goats, and sheep [1]
RVP1 Induces Apoptosis—VP1 of FMDV contains an RGD motif, which is characteristic of the ligands that bind to cellular integrins [4, 8, 36]
Our results show that treatment of BHK-21 cells with both platelet-derived growth factor (PDGF) and glycogen synthase kinase-3 (GSK-3)I attenuated the apoptotic effect of recombinant DNA-derived VP1 (rVP1) in a dose-dependent manner (Fig. 4, A and B)
Summary
Foot-and-mouth disease virus (FMDV)1 is the etiological agent of foot-and-mouth disease, a deadly epidemic that affects many economically important domestic livestock such as cattle, pigs, goats, and sheep [1]. We show that aqueous soluble recombinant DNA-derived VP1 (rVP1) of FMDV induced apoptosis of BHK-21 cells after binding to integrins.
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