New strategies for prevention and control of viral diseases: foot-and-mouth disease virus as a model
Research summary:
Foot-and-mouth disease virus (FMDV) is one of the major concerns for animal health. It is also an interesting model system for understanding the interactions of a highly variable virus and its natural hosts and the implications of these interactions on disease control. We are working in the development of new FMDV peptide marker vaccines that can induce protective humoral and cellular immune responses, using pig and cattle, important domestics hosts, as animal models. We have also analyzed the functional role of FMDV proteins on the viral particle stability and internalization, the replication cycle and the mechanisms mediating the pathogenesis of FMDV and other related viruses causing vesicular diseases, such as swine vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV). Special attention has been paid to the functional implications of nonstructural proteins in virus virulence and host range. The role of different cellular lipids in the multiplication of these and other viruses such as West Nile virus (WNV), responsible for an important zoonosis, have also been addressed. As part of these studies, we have continued collaborating in the characterization of the inhibitory effect of valproic acid and other antiviral compounds targeting cellular metabolism such as lauryl gallate on the multiplication of FMDV and of other enveloped viruses, like African swine fever virus (ASFV) and type I herpesvirus.

Fig. 1.

Last name | Name | Laboratory | Ext.* | Professional category | |
---|---|---|---|---|---|
Bustos Sánchez | Mª José | 105 | 4522 | mjbustos(at)cbm.csic.es | Oficial de Actividades Tecn. y Profes.GP4 |
León Valdés | Patricia Mª de | 105 | 4522 | pdeleon(at)cbm.csic.es | Titulado Sup. Actividades Tecn.y Prof.GP1 |
Sobrino Castelló | Francisco | 415.5 | 4493 | fsobrino(at)cbm.csic.es | E. Profesores de Investigación de Organismos Públicos de Investigación |
Relevant publications:
- Borrego, B., Blanco, E., Rodríguez Pulido, M., Mateos, F., Lorenzo, G., Cardillo, S., Smitsaart, E., Sobrino, F. and Sáiz, M. (2017) Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine. Antiviral Res. 142, 30-36.doi: 10.1016/j.antiviral.2017.03.009.
- Caridi, F., Vázquez-Calvo, A., Borrego, B., McCullough, K., Summerfield, A., Sobrino, F.* and Martín-Acebes, M.A. (2017) Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability. Vet. Microbiol. 203, 275 - 279.doi: 10.1016/j.vetmic.2017.03.
- Bohórquez, J.A., Defaus, S., Muñoz-González, S., Perez-Simó, M., Rosell, R., Fraile, L., Sobrino, F., Andreu, D. and Ganges, L. (2017) A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus. Virus Res. 238, 8-12.doi: 10.1016/j.virusres.2017.05.020.
- Soria, I., Quattrocchi, V., Langellotti, C., Gammella, M., Digiacomo, S., Garcia de la Torre. B., Andreu, D., Montoya, M., Sobrino, F*., Blanco, E. and Zamorano, P. (F. Sobrino, corresponding author). (2017) Dendrimeric peptides can confer protection against foot-and-mouth disease virus in cattle. PLoS ONE 12 (9): e0185184.doi: 10.1371/journal.pone.0185184.
- Blanco, E., Andreu, D. and Sobrino, F. (2017) Peptide vaccines against foot-and-mouth disease virus. In Sobrino, F. and Domigo, E. (eds.) Foot and mouth disease virus: current research and emerging trends. Caister Academic Press, Norfolk, UK. pp.317-332.doi: 10.21775/9781910190517.15.
- Soria, I., Quattrocchi, V., Langellotti, C., Pérez Filgueira, M., Romera, S., Schammas, J., Buscafuco, D., Garcia de la Torre, B., Andreu, D., Sobrino, F*., Blanco, E. and Zamorano, P. (2018) Immune response and partial protection against heterologous foot-and-mouth disease virus induced by dendrimer peptides in cattle. J. Immunol. Res.doi:10.1155/2018/3497401.
- Rodríguez Pulido, M., del Amo, L., Sobrino, F. and Sáiz, M. (2018) Synthetic RNA derived from the foot-and-mouth disease virus genome elicits antiviral responses in bovine and porcine cells through IRF3 activation. Vet. Microbiol. 221, 8-12.doi: 10.1016/j.vetmic.2018.05.015.
- Rodríguez Pulido, M., Sánchez-Aparicio, M.T., Martínez-Salas, E., García-Sastre, A., Sobrino, F. and Sáiz, M. (2018) Innate immune sensor LGP2 is cleaved by the leader protease of foot-and-mouth disease virus. PLoS Pathog. 14(6):e1007135.doi: 10.1371/journal.ppat.1007135.
- de la Higuera, I., Ferrer-Orta, C.; Moreno, E., De Ávila, A., Soria, M.E., Kamlendra, S., Caridi, F., Sobrino, F., Sarafianos, C., Perales, C., Verdaguer, N. and Domingo, E. (2018) Contribution of a multifunctional polymerase region of foot-and-mouth disease virus to lethal mutagenesis. J. Virol. 92:e01119-18.doi: 10.1128/JVI.01119-18.
- de León, P., Bustos, M.J., Torres, E., Cañas-Arranz, R., Sobrino, F*. and Carrascosa, A.L. Inhibition of porcine viruses by different cell-targeted antiviral drugs. Frontiers Microbiol. 10, 1853. doi: 10.3389/fmicb.2019.01853 (2019).
- Gil. M.J., González-González, R., Alvarez-Gutiérrez, A., Martín-Acebes, M.A., Vázquez-Calvo, A., Sáiz, J.C., López-Guerrero, J.A., Tabarés, E. and Sobrino, F*. (F. Sobrino, corresponding author). Herpes virus infections in patients treated with valproic Acid: A nested case-control study in the Spanish primary care database, BIFAP. J. Clin. Med. 8, 1442. doi:10.3390/jcm8091442 (2019).
- Caridi F., López-Arguello, S., Rodriguez-Huete, A., Torres, E., Bustos, M.J., Cañas-Arranz, R., Martín-Acebes, M.A., Mateu, M.G. and Sobrino, F. Introduction in foot-and-mouth disease virus of a negatively charged group at the capsid internal surface reduces the virion-destabilizing effect of the viral RNA at acidic pH. Sci. Rep. (2020) 10:1657. doi.org/10.1038/s41598-020-58414-8 (2020).
- Cañas-Arranz, R., Forner, M., Defaus, de León, P., Bustos, M.J., Torres, E., Andreu, D., Sobrino, F*. and Blanco, E. A single dose of dendrimer B2T peptide vaccine partially protects pigs against foot-and-mouth disease virus infection. Vaccines 2020, 8,19. doi:10.3390/vaccines8010019 (2020).
- Cañas-Arranz, R., Forner, M., Defaus, S., Rodrigez-Pulido, M., de León, P., Torres, E., Bustos, M.J., Borrego, B., Sáiz, M., Blanco, E., Andreu, D. and Sobrino, F. A bivalent B-cell epitope dendrimer peptide can confer long lasting protective immunity in swine against foot-and-mouth disease. Transbound. Emerg. Dis. 2020; 00:1-9. DOI: 10.1111/tbed.13497 (2020).
Doctoral theses:
- Yuri A. Vieira (2015). Contribuciones al estudio de la funcionalidad de las proteínas no estructurales del virus de la fiebre aftosa. Universidad Autónoma de Madrid. Directores: M.F. Rosas y F. Sobrino.
- Flavia Caridi (2017). Bases Moleculares de la estabilidad de la cápsida de los aftovirus. Universidad Autónoma de Madrid. Directores: F. Sobrino y M.A. Martín Acebes. Sobresaliente “Cum Laude”.
Patents:
- Vacunas peptídicas para la prevención de la fiebre aftosa. David Andreu, Juan Bárcena del Riego, Esther Blanco, Carolina Cubillos, Beatriz García de la Torre, Marta Monsó, Francisco Sobrino. P20130101063. Argentina (03/04/2013).
- Peptide vaccines for the prevention of foot-and-mouth disease. David Andreu, Juan Bárcena del Riego, Esther Blanco, Carolina Cubillos, Beatriz García de la Torre, Marta Monsó, Francisco Sobrino.P. number: 2013800289123. P.R.China (01/12/2014).
- Use of esters derived from gallic acid as antivirals. P. de León, A. L. Carrascosa, M.J. Bustos, F. Sobrino. E. Torres, R. Cañas. Patente ES1641.1421 (12-11-2018).
Edited books:
- Sobrino, F. and Domingo, E. (eds) (2017). Foot and mouth disease virus: current research and emerging trends. Caister Academic Press, Norfolk, UK. ISBN: 978-1-910190-51-7 (paperback); 978-1-910190-52-4 (ebook).