Miguel Hernández University Group

Acronym
UMH
Area
Immunology and Diseases Area
Description

The Miguel Hernández University group has focused on establishing the molecular basis governing the protection conferred by vaccines against fish viruses using, among others, genomic and proteomics tools. Several studies have been carried out on the role of autophagy in the response of fish to infections; The processes of epigenetic reprogramming of the innate immune system of fish after infection and / or vaccination have also been studied as well as studies on "memory" in the "trained immunity". Trials of mass vaccination / therapeutic agents (antimicrobial peptides) have also been carried out by immersion bath using nanoparticles of new generation biocompatible polymer materials. All these studies have been possible thanks to the collaborations and interactions carried out with other groups.

Principal investigator
Other members
Dr. A Falcó
Dra. A Martínez
Dr. R Mallavia
Papers SCI

2008. In vitro search for alternative promoters to the human immediate early cytomegalovirus (IE-CMV) to express the G gene of viral haemorrhagic septicemia virus (VHSV) in fish epithelial cells. Vaccine 26: 6620–29. Ruiz S, Tafalla C, Cuesta A, Estepa A, Coll JM.

 

2008. Inhibitory effect of mycophenolic acid on the replication of infectious pancreatic necrosis virus and viral hemorrhagic septicemia virus. Antiviral Res 80: 332–38. Marroqui L, Estepa A, Perez L.

 

2009. New tools to study RNA interference to fish viruses: Fish cell lines permanently expressing siRNAs targeting the viral polymerase of viral hemorrhagic septicemia virus. Antiviral Res 82: 148-56. Ruiz S, Schyth BD, Encinas P, Tafalla C, Estepa A, Lorenzen N, Coll JM.

 

2009. Transfection improvements of fish cell lines by using deacylated polyethylenimine of selected molecular weights. Fish Shellfish Immunol 26: 559-66. Falco A, Encinas P, Carbajosa S, Cuesta A, Chaves-Pozo E, Tafalla C, Estepa A, Coll JM.

 

2009. The immunogenicity of viral hemorrhagic septicaemia rhabdovirus (VHSV) DNA vaccines can depend on plasmid regulatory sequences. Vaccine 27: 1938-48. Chico V, Ortega-Villaizan M, Falco A, Tafalla C, Perez L, Coll JM, Estepa A.

 

2009. The rainbow trout TLR9 gene and its role in the immune responses elicited by a plasmid encoding the glycoprotein G of the viral haemorrhagic septicaemia rhabdovirus (VHSV). Mol Immunol 46(8-9): 1710-17. Ortega-Villaizan M, Chico V, Falco A, Perez L, Coll JM, Estepa A.

 

2009. Antimicrobial peptides as model molecules for the development of novel antiviral agents in aquaculture. Mini Rev Med Chem 9(10): 1159-64. Falco A, Ortega-Villaizan M, Chico V, Brocal I, Perez L, Coll JM, Estepa A.

 

2009. Nodavirus infection of sea bass (Dicentrarchus labrax) induces up-regulation of galectin-1 expression with potential anti-inflammatory activity. J Immunol 183(10): 6600-11. Poisa-Beiro L, Dios S, Ahmed H, Vasta GR, Martínez-López A, Estepa A, Alonso-Gutiérrez J, Figueras A, Novoa B.

 

2010. Zebrafish fin immune responses during high mortality infections with viral haemorrhagic septicemia rhabdovirus. A proteomic and transcriptomic approach. BMC Genomics 11: 518-534.  Encinas P, Rodríguez-Milla M A, Novoa B, Estepa A, Figueras A, Coll J.

 

2010. Pepscan mapping of Viral Hemorrhagic Septicemia Virus glycoprotein G major lineal determinants implicated in triggering host cell antiviral responses mediated by type I Interferon. J Virol 84: 7140-7150. Chico V, Martínez-López A, Ortega-Villaizan M, Falcó A, Pérez L, Coll JM, Estepa A.

 

2011. Rainbow trout surviving infections of viral haemorrhagic septicemia virus (VHSV) show lasting antibodies to recombinant G protein fragments. Fish Shellfish Immunol 30: 929-35.  Encinas P, Gomez-Casado E, Fregeneda-Grandes, Olesen NJ, Lorenzen N, Estepa A, Coll JM.

 

2011. A comparative review on European-farmed finfish RNA viruses and their vaccines. Vaccine 29: 2657-71.  Gomez-Casado E, Estepa A, Coll JM.

 

2011. In vitro analysis of the factors contributing to the antiviral state induced by a plasmid encoding the viral haemorrhagic septicaemia virus glycoprotein G in transfected trout cells. Vaccine 29: 737-43. Ortega-Villaizan M, Chico V, Martinez-Lopez A, Falco A, Perez L, Coll JM, Estepa A.

 

2012. Ex vivo transfection of trout pronephros leukocytes, a model for cell culture screening of fish DNA vaccine candidates. Vaccine 30: 5983-90. Ortega-Villaizan M, Martinez-Lopez A, Garcia-Valtanen P, Chico V, Perez L, Coll J, Estepa A

 

2012. Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV). J Biotechnol 164: 171-78. Martinez-Lopez A, Chinchilla B, Encinas P, Gomez-Casado E, Estepa A, Coll J.

 

2013. Improving the safety of viral DNA vaccines: development of vectors containing both 5' and 3' homologous regulatory sequences from non-viral origin. Appl Microbiol Biotechnol 97(7): 3007-16. Martinez-Lopez A, Encinas P, Garcia-Valtanen P, Gomez-Casado E, Coll J M, Estepa A.

 

2013. Melittin-loaded immunoliposomes against viral surface proteins, a new approach to antiviral therapy. Antiviral Res 97(2): 218-21. Falco A, Barrajon-Catalan E, Menendez-Gutierrez MP, Coll J, Micol V, Estepa A.

 

2013. In vitro neutralization of viral hemorrhagic septicemia virus by plasma from immunized zebrafish. Zebrafish 10: 43-51. Chinchilla B, Gomez-Casado E, Encinas P, Falco A, Estepa A, Coll J.

 

2013. Identification of multipath genes differentially expressed in pathway-targeted microarrays in zebrafish infected and surviving Spring Viremia Carp Virus (SVCV) Suggest preventive drug candidates. PLoS One 8: e73553. Encinas P, Garcia-Valtanen P, Chinchilla B, Gomez-Casado E, Estepa A, Coll J.

 

2013. Increasing versatility of the DNA vaccines through modification of the subcellular location of plasmid-encoded antigen expression in the in vivo transfected cells. PLoS One 8: e77426. Martinez-Lopez A, Garcia-Valtanen P, Ortega-Villaizan M, Chico V, Medina-Gali RM, Perez L, Coll J, Estepa A.

 

2013. Behavioural fever is a synergic signal amplifying the innate immune response. Proc Royal Soc B Biol Sciences 280. Boltaña S, Rey S, Roher N, Vargas R, Huerta M, Huntingford FA, Goetz FW, Moore J, Garcia-Valtanen P, Estepa A, MacKenzie S.

 

2013. pH-dependent solution structure and activity of a reduced form of the host-defense peptide myticin C (Myt C) from the mussel Mytilus galloprovincialis. Marine Drugs 11: 2328-46. Martinez-Lopez A, Encinar JA, Medina-Gali RM, Balseiro P, Garcia-Valtanen P, Figueras A, Novoa B, Estepa A.

 

2013. Optimization of fixed-permeabilized cell monolayers for high throughput micro-neutralizing antibody assays: application to the zebrafish/viral hemorrhagic septicemia virus (VHSV) model. J Virol Methods 193: 627-32. Chinchilla B, Gomez-Casado E, Encinas P, Falco A, Estepa A, Coll J.

 

2013. Antiviral activity produced by an IPNV-carrier EPC cell culture confers resistance to VHSV infection. Vet Microbiol 166: 412-18. Jurado MT, García-Valtanen P, Estepa A, Perez L.

 

2014. In addition to its antiviral and immunomodulatory properties, the zebrafish b-defensin 2 (zfBD2) is a potent viral DNA vaccine molecular adjuvant. Antiviral Res 101: 136-47. García-Valtanen P, Martinez-Lopez A, Ortega-Villaizan M, Perez L, Coll J, Estepa A.

 

2014. Autophagy-inducing peptides from mammalian VSV and fish VHSV rhabdoviral G glycoproteins (G) as models for the development of new therapeutic molecules. Autophagy 10: 1666-80. Garcia-Valtanen P, Ortega-Villaizan MM, Martinez-Lopez A, Medina-Gali R, Perez L, Mackenzie S, Figueras A, Coll JM, Estepa A.

 

2014. VHSV G glycoprotein major determinants implicated in triggering the host type I IFN antiviral response as DNA vaccine molecular adjuvants. Vaccine 32: 6012-19. Martinez-Lopez A, Garcia-Valtanen P, Ortega-Villaizan M, Chico V, Casado E, Coll JM, Estepa A.

 

2014. Transcriptome profiles associated to VHSV infection or DNA vaccination in turbot (Scophthalmus maximus). PLoS One 9(8): e104509. Pereiro P, Dios S, Boltaña S, Coll J, Estepa A, Mackenzie S, Novoa B, Figueras A.

 

2015. Transcriptome analysis of rainbow trout in response to non-virion (NV) protein of viral hemorrhagic septicemia virus (VHSV). Applied Microbiol Biotechnol 99(4):1 827-43. Chinchilla B, Encinas P, Estepa A, Coll JM, Gomez-Casado E.

 

2015. Inhibition of SERPINe1 reduces rhabdoviral infections in zebrafish. Fish Shellfish Immunol. 47(1):264-70. Estepa A, Coll J.

 

2015. Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype. PLoS One. 13;10(8): e0135483.  Estepa A, Coll J. 

 

2015. Development of new therapeutical/adjuvant molecules by pepscan mapping of autophagy and IFN inducing determinants of rhabdoviral G proteins. Mol Immunol. 70:118-24. Ortega-Villaizan M, Chico V, Martinez-Lopez A, Garcia-Valtanen P, Coll JM, Estepa A.

 

2015. Innate Multigene Family Memories Are Implicated in the Viral-Survivor Zebrafish Phenotype. PLoS One. 13;10(8): e0135483. Estepa A, Coll J. 

 

2016. Inhibition of SERPINe1 reduces rhabdoviral infections in zebrafish. Fish Shellfish Immunol. 47(1):264-70.  Estepa A, Coll J.

 

2016. Development of new therapeutical/adjuvant molecules by pepscan mapping of autophagy and IFN inducing determinants of rhabdoviral G proteins. Mol Immunol. 70:118-24. Ortega-Villaizan M, Chico V, Martinez-Lopez A, Garcia-Valtanen P, Coll JM, Estepa A.

 

2016. TNFα impairs rhabdoviral clearance by inhibiting the host autophagic antiviral response. Plos Pathog. 28;12(6): e1005699. Espín-Palazón R, Martínez-López A, Roca FJ, López-Muñoz A, Tyrkalska SD, Candel S, García-Moreno D, Falco A, Meseguer J, Estepa A, Mulero V.

Books & Books Chapters

2008. Defence mechanisms against viral infections in fish: the trout/ viral haemorrhagic septicaemia (VHSV) rhabdovirus model. In Fish Defences: Fish Armament and Secretions Vol 2. (Eds.) G. Zaccone, MJ. Manning, CJ. Secombes and BG. Kapoor. Science publishers. USA. (ISBN-13: 9781578084074).  Estepa A, Tafalla C, Coll JM.

 

2010. Antigenicity and Immunogenicity of the Envelope Glycoprotein (gpG) of Viral Haemorrhagic Septicaemia Rhabdovirus. Chapter 2. Ed: C.J. Villanueva (ISBN: 978-1-61761-591-7) Immunogenicity. 2010 Nova Science PUBlishers, Inc. Falcó A, Ortega-Villaizan M, Coll JM, Estepa A.

 

2011. Use of microarray technology to improve DNA vaccines in fish aquaculture: the rhabdoviral model. Aquaculture, INTECH, Croatia. 2011; Book 2, chapter 4:1-18.

Patents

Intraperiotenal recombinant DNA vaccine against VHSV.

 

Papers (non-SCI)

2011. Possible applications to aquaculture of salmonid sleeping beauty transposon vectors. Dynamic Biochemistry, Process Biotechnology and Molecular Biology Aquaculture 2: 34-45

2011. Antibody recognition of the protein G of viral haemorrhagic septicemia virus purified in large amount from insect larvae. BMC reports. 4:210-7

Conference communications (participation)

2008. Pepscan mapping of the major type I IFN-inducing regions in viral haemorrhagic septicaemia rhabdovirus (VHSV)- G glycoprotein. XIV International congress of virology. Estambul (Turkey) 10-15 August. Chico V, Ortega-Villaizan Romo M, Falcó A, Brocal I, Pérez L, Coll JM, Estepa A. Chico V, Ortega-Villaizan Romo M, Falcó A, Brocal I, Pérez L, Coll JM, Estepa A.

 

2008. In vitro efficacy of ribavirin and mycophenolic acid against rainbow trout viruses IPNV and VHSV. The 7th symposium on diseases in Asian aquaculture. Taipei (Taiwan) 22-29 June. Perez L, Marroqui L, Chico Gras V, Ortega-Villaizan Romo M, Estepa A. Perez L, Marroqui L, Chico Gras V, Ortega-Villaizan Romo M, Estepa A.

2008. Induction of type I interferon by VHSV: role of surface glycoprotein G. 5TH International conference on innate immunity. Creta (Greece) 19-22 June. Chico V, Ortega-Villaizan Romo M, Pérez L, Mallavia R, Coll JM, Estepa A. Chico V, Ortega-Villaizan Romo M, Pérez L, Mallavia R, Coll JM, Estepa A.                      

 

2009. Role of trout myocytes in the immune response elicited by fish DNA vaccines administered by intramuscular injection. Genomics in Aquaculture, GIA 2009. Bodo, Norway. 1-5 September. Falco A, Vraskou Y, Chico V, Ortega-Villaizan M., Martinez-Lopez A, Perez L, Planas JV, Estepa A. Falco A, Vraskou Y, Chico V, Ortega-Villaizan M., Martinez-Lopez A, Perez L, Planas JV, Estepa A.

 

2010. In vitro analysis of rainbow trout TLR9 implication in cell resistance to viral haemorrhagic septicaemia rhabdovirus (VHSV) infection conferred by CpGs ODNs, plasmid DNA and transfected VHSV glycoprotein G. 8th International Symposium on viruses of lower vertebrates. 29-29 April. Ortega-Villaizan M; Chico V; Martinez-Lopez A; Perez L; Coll, JM; Coll; JM. And Estepa; A

 

2010. In vitro analysis of raINBow trout TLR9 implication in cell resistance to viral haemorrhagic septicaemia rhabdovirus (VHSV) infection conferred by CpGs ODNs, plasmid DNA and transfected VHSV glycoprotein G. 8th International Symposium on viruses of lower vertebrates. 29-29 April. Ortega-Villaizan M; Chico V; Martinez-Lopez A; Perez L; Coll, JM; Coll; JM. And Estepa; A

 

2010. Molecular and cellular characterization of the antiviral protection from the EPC cell lines permanently expressing raINBow trout beta-defensin. 8th International Symposium on viruses of lower vertebrates. 29-29 April. Falcó A; Martinez-Lopez A; Chico V.; Ortega-Villaizan M; Pérez L; Martinez-Lopez A.; L.; Coll; JM: and Estepa; A.

 

2010. A first approach on plasmid DNA transfection of an ex vivo rainbow trout pronephros cells culture. First EOFFI symposium. Viterbo (Italy), 23-27 May. Ortega-Villaizan M.; Chico V.; Martinez-Lopez A.; Perez L.; Coll J. Estepa A

 

2010. Nodavirus infection of sea bass (Dicentrarchus labrax) induces upregulation of galectin-1 expression with potential anti-inflammatory activity. 8TH International symposium on virus of lower vertebrates. Santiago de Compostela (Spain), 26-29 April. Poisa-Beiro L, Dios S, Ahmed H, Vasta GR, Martínez-López A, Estepa A, Alonso-Gutiérrez J, Figueras A, Novoa B

 

2010. Improvement of aquaculture production by the use of biotechnological tools (AQUAGENOMICS). Aquaculture Europe 2010. Porto (Portugal), 5-8 October. Novoa B, Martínez P, Piferrer F, Mackenzie S, Planas JV, Morán F, Toranzo AE, Mulero V, Sanchez FJ, Estepa A, Coll J, Tort L, Yufera M, Pérez J, Zanuy S, Cerdá JM, Toro MA, Rejón MR, Figueras A

       

 

2011. Efficacy of a DNA-vaccine against viral hemorrhagic septicaemia virus (VHSV) in turbot (Psetta maxima). 15TH EAFP International Conference on Diseases of Fish and Shellfish 2011; Split (Croatia), 12-16 September. Novoa B, Dios S, Pereiro P, Coll J, Figueras A, Estepa A.

 

2012. The potential for antimicrobial peptides to improve fish health in aquaculture. Infectious disease in aquaculture (ISBN: 978-0-85709-016-4). Capítulo 17. pp 457-479. Falco A, Martinez-López A, Coll JM, Estepa A.

2012. Use of microarray technology to improve DNA vaccines in fish aquaculture: the rhabdoviral model. Health and environment in Aquaculture, INTECH, Croatia ed.E.D.Carvalho, G.S.David, and R.J.da Silva. ISBN 978-953-51-0497-1 (2012). Chapter 10, 251-276. Encinas P, Gomez-Casado E, Estepa A, Coll JM

2013. The use of zebrafish as a model system for development of new adjuvant strategies in finfish DNA vaccination against viruses. Immunology 2013™ AAI Annual Meeting. Honolulu (Hawaii) 03-07 May. Arnemo M., Kavaliauskis A, Estepa A, Dios S, Novoa B, Gjøen T (UMH, IIM)

2013. Use of an immune-specific microarray for identifying transcriptome profiles associated to the infection of VHSV or to the protection mechanisms induced by a DNA vaccine encoding the G glycoprotein in turbot (Scophthalmus maximus). First International Conference of Fish and Shellfish Immunology (ISFSI). Vigo (Spain), 25-28 June. Pereiro P, Boltaña S, Dios S, Coll J, Estepa A, Mackenzie S, Novoa B, Figueras A

2013. pH-dependent solution structure and antimicrobial activity of myt c. First International Conference of Fish and Shellfish Immunology (ISFSI). Vigo (Spain), 25-28 June. Martinez-López A, Medina-Gali RM, Balseiro P, Figueras A, Encinar JA, Novoa B, Estepa A.

2013. Zebrafish differential transcriptomic profiles induced by VHSV and SVCV G glycoproteins after genetic immunization. First International Conference of Fish and Shellfish Immunology (ISFSI). Vigo (Spain), 25-28 June. García-Valtanen P, Martínez-López A Ortega-Villaizán M, Cheikh SI, Pérez L, Coll J, Mackenzie S, Figueras A, Estepa A.

Thesis

2010. Verónica Chico Gras. University Miguel Hernández. Optimización de Vacunas DNA frente a rhabdovirus de peces: análisis del antígeno y del vector. Supervisor Estepa A.

2014. Pablo Garcia Valtanen. University Miguel Hernández. Using host- and virus-derived molecules to design new antiviral strategies against rhabdoviruses. Supervisor Estepa A.

Participation in another related projects

ERC Starting Grant. BloodCellsCrosstalk. The crosstalk between red and white blood cells: The case of fish

Industry collaboration

Technical assistance for the antimicrobial peptide analysis. Company LABIOFAM S.A. (CUBA).

Nanoparticles for viral DNA vaccines. Company LIPOTEC S.A.

 

Stays in another labs

Regla María Medina Gali visted the Instituto de Investigaciones Marinas (Vigo).  05/11/2016-04/12/2016.

Melissa Belló Pérez visted the Instituto de Investigaciones Marinas (Vigo). 23/10/2016-25/11/2016.