Interferon lambda protects cattle against bovine viral diarrhea virus infection

Interferon lambda (IFN-λ) plays an important role in inducing an antiviral state in mucosal surfaces and has been used as an effective biotherapeutic against several viral diseases. Here we performed a proof of concept study on the activity of a biologically active recombinant bovine IFN-λ (rIFN-λ)...

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Autores principales: Quintana, Maria Eugenia, Cardoso, Nancy, Pereyra, Walter Rodrigo, Barone, Lucas Jose, Barrionuevo, Florencia Mariel, Mansilla, Florencia Celeste, Turco, Cecilia Soledad, Capozzo, Alejandra
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2021
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12123/8582
https://www.sciencedirect.com/science/article/abs/pii/S0165242720301719
https://doi.org/10.1016/j.vetimm.2020.110145
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author Quintana, Maria Eugenia
Cardoso, Nancy
Pereyra, Walter Rodrigo
Barone, Lucas Jose
Barrionuevo, Florencia Mariel
Mansilla, Florencia Celeste
Turco, Cecilia Soledad
Capozzo, Alejandra
author_browse Barone, Lucas Jose
Barrionuevo, Florencia Mariel
Capozzo, Alejandra
Cardoso, Nancy
Mansilla, Florencia Celeste
Pereyra, Walter Rodrigo
Quintana, Maria Eugenia
Turco, Cecilia Soledad
author_facet Quintana, Maria Eugenia
Cardoso, Nancy
Pereyra, Walter Rodrigo
Barone, Lucas Jose
Barrionuevo, Florencia Mariel
Mansilla, Florencia Celeste
Turco, Cecilia Soledad
Capozzo, Alejandra
author_sort Quintana, Maria Eugenia
collection INTA Digital
description Interferon lambda (IFN-λ) plays an important role in inducing an antiviral state in mucosal surfaces and has been used as an effective biotherapeutic against several viral diseases. Here we performed a proof of concept study on the activity of a biologically active recombinant bovine IFN-λ (rIFN-λ) produced in eukaryotic cells against Bovine Viral Diarrhea Virus (BVDV) in cattle. We first confirmed the lack of toxicity of different concentrations of rIFN-λ in bovine peripheral blood cells and the safety of its subcutaneous application in calves in doses up to 12 IU/kg. The antiviral activity of the rIFN-λ against BVDV was assessed in calves that were inoculated with 6 IU/kg of rIFN-λ (n = 4) or mock-treated (n = 2) two days before and after challenge with a BVDV type-2 non-cytopathic strain. Mock-treated animals developed respiratory disease, shedded the virus from 4 to 7 days post-infection (dpi) and had viremia between 4 and 14 dpi. Conversely, calves treated with rIFN-λ did not develop clinical symptoms. The virus was not found in nasal secretions or sera. Only one animal had a positive viral RNA detection in serum at 7 dpi. All infected animals treated with rIFN-λ increased systemic type-I IFNs levels at 4 dpi. The antiviral treatment induced an earlier onset of the anti-BVDV neutralizing antibodies. Altogether, these results constitute the proof-of-principle of bovine IFN-λ as an antiviral biotherapeutic to protect cattle against the clinical disease caused by BVDV.
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institution Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina)
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spelling INTA85822021-03-09T15:11:19Z Interferon lambda protects cattle against bovine viral diarrhea virus infection Quintana, Maria Eugenia Cardoso, Nancy Pereyra, Walter Rodrigo Barone, Lucas Jose Barrionuevo, Florencia Mariel Mansilla, Florencia Celeste Turco, Cecilia Soledad Capozzo, Alejandra Interferons Bovine Viral Diarrhoea Disease Control Antiviral Agents Cattle Interferonas Diarrea Viral Bovina Control de Enfermedades Viricidas Ganado Bovino Interferon lambda (IFN-λ) plays an important role in inducing an antiviral state in mucosal surfaces and has been used as an effective biotherapeutic against several viral diseases. Here we performed a proof of concept study on the activity of a biologically active recombinant bovine IFN-λ (rIFN-λ) produced in eukaryotic cells against Bovine Viral Diarrhea Virus (BVDV) in cattle. We first confirmed the lack of toxicity of different concentrations of rIFN-λ in bovine peripheral blood cells and the safety of its subcutaneous application in calves in doses up to 12 IU/kg. The antiviral activity of the rIFN-λ against BVDV was assessed in calves that were inoculated with 6 IU/kg of rIFN-λ (n = 4) or mock-treated (n = 2) two days before and after challenge with a BVDV type-2 non-cytopathic strain. Mock-treated animals developed respiratory disease, shedded the virus from 4 to 7 days post-infection (dpi) and had viremia between 4 and 14 dpi. Conversely, calves treated with rIFN-λ did not develop clinical symptoms. The virus was not found in nasal secretions or sera. Only one animal had a positive viral RNA detection in serum at 7 dpi. All infected animals treated with rIFN-λ increased systemic type-I IFNs levels at 4 dpi. The antiviral treatment induced an earlier onset of the anti-BVDV neutralizing antibodies. Altogether, these results constitute the proof-of-principle of bovine IFN-λ as an antiviral biotherapeutic to protect cattle against the clinical disease caused by BVDV. Instituto de Virología Fil: Quintana, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Pereyra Walter Rodrigo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Barrionuevo, Florencia Mariel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Turco Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2021-01-08T16:14:54Z 2021-01-08T16:14:54Z 2020-12 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/8582 https://www.sciencedirect.com/science/article/abs/pii/S0165242720301719 0165-2427 https://doi.org/10.1016/j.vetimm.2020.110145 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Veterinary Immunology and Immunopathology 230 : 110145 (Diciembre 2020)
spellingShingle Interferons
Bovine Viral Diarrhoea
Disease Control
Antiviral Agents
Cattle
Interferonas
Diarrea Viral Bovina
Control de Enfermedades
Viricidas
Ganado Bovino
Quintana, Maria Eugenia
Cardoso, Nancy
Pereyra, Walter Rodrigo
Barone, Lucas Jose
Barrionuevo, Florencia Mariel
Mansilla, Florencia Celeste
Turco, Cecilia Soledad
Capozzo, Alejandra
Interferon lambda protects cattle against bovine viral diarrhea virus infection
title Interferon lambda protects cattle against bovine viral diarrhea virus infection
title_full Interferon lambda protects cattle against bovine viral diarrhea virus infection
title_fullStr Interferon lambda protects cattle against bovine viral diarrhea virus infection
title_full_unstemmed Interferon lambda protects cattle against bovine viral diarrhea virus infection
title_short Interferon lambda protects cattle against bovine viral diarrhea virus infection
title_sort interferon lambda protects cattle against bovine viral diarrhea virus infection
topic Interferons
Bovine Viral Diarrhoea
Disease Control
Antiviral Agents
Cattle
Interferonas
Diarrea Viral Bovina
Control de Enfermedades
Viricidas
Ganado Bovino
url http://hdl.handle.net/20.500.12123/8582
https://www.sciencedirect.com/science/article/abs/pii/S0165242720301719
https://doi.org/10.1016/j.vetimm.2020.110145
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