In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model

Autores
Quintana, Maria Eugenia; Barone, Lucas Jose; Trotta, Myrian Vanesa; Turco, Cecilia Soledad; Mansilla, Florencia Celeste; Capozzo, Alejandra; Cardoso, Nancy
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.
Instituto de Virología
Fil: Quintana, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Trotta, Myrian Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Turco, Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Quintana, María Eugenia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
Fil: Barone, Lucas Jose. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina
Fil: Capozzo, Alejandra Victoria.Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
Fil: Cardoso, Nancy Patricia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
Fuente
Frontiers in veterinary science 7 : 45. (Febrero 2020)
Materia
Bovine Diarrhoea Pestivirus
Interferons
Antiviral Agents
Pestivirus de la Diarrea Bovina
Interferonas
Viricidas
Mouse Model
Modelo de Ratón
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/8606
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oai_identifier_str oai:localhost:20.500.12123/8606
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network_name_str INTA Digital (INTA)
spelling In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse modelQuintana, Maria EugeniaBarone, Lucas JoseTrotta, Myrian VanesaTurco, Cecilia SoledadMansilla, Florencia CelesteCapozzo, AlejandraCardoso, NancyBovine Diarrhoea PestivirusInterferonsAntiviral AgentsPestivirus de la Diarrea BovinaInterferonasViricidasMouse ModelModelo de RatónBovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.Instituto de VirologíaFil: Quintana, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.Fil: Trotta, Myrian Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Turco, Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.Fil: Quintana, María Eugenia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); ArgentinaFil: Barone, Lucas Jose. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Capozzo, Alejandra Victoria.Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); ArgentinaFil: Cardoso, Nancy Patricia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); ArgentinaFrontiers Media2021-01-15T15:11:54Z2021-01-15T15:11:54Z2020-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/8606https://www.frontiersin.org/articles/10.3389/fvets.2020.00045/full2297-1769https://doi.org/10.3389/fvets.2020.00045Frontiers in veterinary science 7 : 45. (Febrero 2020)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-10-30T11:23:34Zoai:localhost:20.500.12123/8606instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-30 11:23:34.611INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
title In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
spellingShingle In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
Quintana, Maria Eugenia
Bovine Diarrhoea Pestivirus
Interferons
Antiviral Agents
Pestivirus de la Diarrea Bovina
Interferonas
Viricidas
Mouse Model
Modelo de Ratón
title_short In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
title_full In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
title_fullStr In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
title_full_unstemmed In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
title_sort In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
dc.creator.none.fl_str_mv Quintana, Maria Eugenia
Barone, Lucas Jose
Trotta, Myrian Vanesa
Turco, Cecilia Soledad
Mansilla, Florencia Celeste
Capozzo, Alejandra
Cardoso, Nancy
author Quintana, Maria Eugenia
author_facet Quintana, Maria Eugenia
Barone, Lucas Jose
Trotta, Myrian Vanesa
Turco, Cecilia Soledad
Mansilla, Florencia Celeste
Capozzo, Alejandra
Cardoso, Nancy
author_role author
author2 Barone, Lucas Jose
Trotta, Myrian Vanesa
Turco, Cecilia Soledad
Mansilla, Florencia Celeste
Capozzo, Alejandra
Cardoso, Nancy
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Bovine Diarrhoea Pestivirus
Interferons
Antiviral Agents
Pestivirus de la Diarrea Bovina
Interferonas
Viricidas
Mouse Model
Modelo de Ratón
topic Bovine Diarrhoea Pestivirus
Interferons
Antiviral Agents
Pestivirus de la Diarrea Bovina
Interferonas
Viricidas
Mouse Model
Modelo de Ratón
dc.description.none.fl_txt_mv Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.
Instituto de Virología
Fil: Quintana, María Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Trotta, Myrian Vanesa. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Turco, Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina
Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina.
Fil: Quintana, María Eugenia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
Fil: Barone, Lucas Jose. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentina
Fil: Capozzo, Alejandra Victoria.Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
Fil: Cardoso, Nancy Patricia. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET); Argentina
description Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre- and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.
publishDate 2020
dc.date.none.fl_str_mv 2020-02
2021-01-15T15:11:54Z
2021-01-15T15:11:54Z
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/8606
https://www.frontiersin.org/articles/10.3389/fvets.2020.00045/full
2297-1769
https://doi.org/10.3389/fvets.2020.00045
url http://hdl.handle.net/20.500.12123/8606
https://www.frontiersin.org/articles/10.3389/fvets.2020.00045/full
https://doi.org/10.3389/fvets.2020.00045
identifier_str_mv 2297-1769
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in veterinary science 7 : 45. (Febrero 2020)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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