title: Foot-and-mouth disease virus infection of dendritic cells triggers phosphorylation 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 pathology is caused by foot-and-mouth disease virus (FMDV). Over time, the development of vaccines to prevent the spread of this illness became essential. Vaccines currently used contain the inactivated form of the virus. However, vaccination generates an immune response different to that induced by the infection. We investigated 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 of ERK1/2, which was involved in the activation of caspase-9, the intrinsic pathway of apoptosis and the delivery of viral peptides on MHC class I molecules. While, inactivated virus (iFMDV) did not affect this pathway or any function mediated by its activation. As described, infectious virus in DCs was also associated to autophagy LC3 protein and was associated to lysosomal protein Lamp-2; contrary to observe for the iFMDV. Strikingly, the processing of viral antigens to accommodate in class I molecules does not appear to involve the proteasome. Finally, this increased presentation promotes a specific cytotoxic response against infectious virus.
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnología Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: langellotti.cecilia@inta.gob.ar.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Langellotti
authors.affiliation: Laboratorio de Inmunología, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Cesar
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnología Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Ivana
authors.initials: I
authors.lastname: Soria
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnología Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina.
authors.forename: Valeria
authors.initials: V
authors.lastname: Quattrocchi
authors.affiliation: Laboratorio de Inmunología, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Jancic
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnología Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Zamorano
authors.affiliation: Laboratorio de Inmunología, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: mvermeulen@hematologia.anm.edu.ar.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vermeulen
mesh_terms: D000818:Animals; D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008807:Mice, Inbred BALB C; D010766:Phosphorylation
chemical_list: D015395:Histocompatibility Antigens Class I; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Caspase-9; Class I-restricted presentation; Cytotoxicity; Dendritic cells; ERK1/2 MAPK; Foot-and-mouth disease virus; Inactive viral particles