In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model
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...
| Autores principales: | , , , , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
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Frontiers Media
2021
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| Materias: | |
| Acceso en línea: | 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 |
| _version_ | 1855036066618146816 |
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| author | Quintana, Maria Eugenia Barone, Lucas Jose Trotta, Myrian Vanesa Turco, Cecilia Soledad Mansilla, Florencia Celeste Capozzo, Alejandra Cardoso, Nancy |
| author_browse | Barone, Lucas Jose Capozzo, Alejandra Cardoso, Nancy Mansilla, Florencia Celeste Quintana, Maria Eugenia Trotta, Myrian Vanesa Turco, Cecilia Soledad |
| author_facet | Quintana, Maria Eugenia Barone, Lucas Jose Trotta, Myrian Vanesa Turco, Cecilia Soledad Mansilla, Florencia Celeste Capozzo, Alejandra Cardoso, Nancy |
| author_sort | Quintana, Maria Eugenia |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA8606 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA86062021-01-15T15:21:46Z In-vivo activity of IFN-λ and IFN-α against bovine-viral-diarrhea virus in a mouse model Quintana, Maria Eugenia Barone, Lucas Jose Trotta, Myrian Vanesa Turco, Cecilia Soledad Mansilla, Florencia Celeste Capozzo, Alejandra Cardoso, Nancy Bovine Diarrhoea Pestivirus Interferons Antiviral Agents Pestivirus de la Diarrea Bovina Interferonas Viricidas Mouse Model Modelo de Ratón 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 2021-01-15T15:11:54Z 2021-01-15T15:11:54Z 2020-02 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf Frontiers Media Frontiers in veterinary science 7 : 45. (Febrero 2020) |
| spellingShingle | Bovine Diarrhoea Pestivirus Interferons Antiviral Agents Pestivirus de la Diarrea Bovina Interferonas Viricidas Mouse Model Modelo de Ratón Quintana, Maria Eugenia Barone, Lucas Jose Trotta, Myrian Vanesa Turco, Cecilia Soledad Mansilla, Florencia Celeste Capozzo, Alejandra Cardoso, Nancy 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 |
| 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_short | 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 |
| topic | Bovine Diarrhoea Pestivirus Interferons Antiviral Agents Pestivirus de la Diarrea Bovina Interferonas Viricidas Mouse Model Modelo de Ratón |
| 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 |
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