Foot-and-mouth disease virus infection of dendritic cells triggersphosphorylation of ERK1/2 inducing class I presentation and apoptosis

Abstract

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. This pathol-ogy is caused by foot-and-mouth disease virus (FMDV). Over time, the development of vaccines to preventthe spread of this illness became essential. Vaccines currently used contain the inactivated form of thevirus. However, vaccination generates an immune response different to that induced by the infection. Weinvestigated whether these differences are related to intracellular mechanisms on dendritic cells (DCs).As a result, we demonstrated that the internalization of infective virus triggered the phosphorylation ofERK1/2, which was involved in the activation of caspase-9, the intrinsic pathway of apoptosis and thedelivery of viral peptides on MHC class I molecules. While, inactivated virus (iFMDV) did not affect thispathway or any function mediated by its activation. As described, infectious virus in DCs was also asso-ciated to autophagy LC3 protein and was associated to lysosomal protein Lamp-2; contrary to observefor the iFMDV. Strikingly, the processing of viral antigens to accommodate in class I molecules doesnot appear to involve the proteasome. Finally, this increased presentation promotes a specific cytotoxicresponse against infectious virus.