Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro

Autores
Cardoso, Nancy; Mansilla, Florencia Celeste; Benedetti, Estefanía; Turco, Cecilia Soledad; Barone, Lucas Jose; Iserte, Javier Alonso; Soria, Ivana; Baumeister, Elsa; Capozzo, Alejandra
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Interferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2.
Instituto de Virología
Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benedetti, Estefanía. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; Argentina
Fil: Turco Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iserte, Javier Alonso. Fundación Instituto Leloir. Structural Bioinformatics Group; Argentina
Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baumeister, Elsa. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; Argentina
Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Frontiers in Veterinary Science 7 : 603622 (Noviembre 2020)
Materia
COVID-19
Interferonas
Viricidas
Virus
Interferons
Antiviral Agents
Viruses
In vitro
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
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network_name_str INTA Digital (INTA)
spelling Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitroCardoso, NancyMansilla, Florencia CelesteBenedetti, EstefaníaTurco, Cecilia SoledadBarone, Lucas JoseIserte, Javier AlonsoSoria, IvanaBaumeister, ElsaCapozzo, AlejandraCOVID-19InterferonasViricidasVirusInterferonsAntiviral AgentsVirusesIn vitroInterferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2.Instituto de VirologíaFil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benedetti, Estefanía. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; ArgentinaFil: Turco Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iserte, Javier Alonso. Fundación Instituto Leloir. Structural Bioinformatics Group; ArgentinaFil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baumeister, Elsa. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; ArgentinaFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFrontiers Media2021-01-08T18:28:54Z2021-01-08T18:28:54Z2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://www.frontiersin.org/articles/10.3389/fvets.2020.603622/fullhttp://hdl.handle.net/20.500.12123/85882297-1769https://doi.org/10.3389/fvets.2020.603622Frontiers in Veterinary Science 7 : 603622 (Noviembre 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)2025-10-16T09:29:59Zoai:localhost:20.500.12123/8588instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-16 09:29:59.991INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
title Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
spellingShingle Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
Cardoso, Nancy
COVID-19
Interferonas
Viricidas
Virus
Interferons
Antiviral Agents
Viruses
In vitro
title_short Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
title_full Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
title_fullStr Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
title_full_unstemmed Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
title_sort Bovine interferon lambda Is a potent antiviral against SARS-CoV-2 infection in vitro
dc.creator.none.fl_str_mv Cardoso, Nancy
Mansilla, Florencia Celeste
Benedetti, Estefanía
Turco, Cecilia Soledad
Barone, Lucas Jose
Iserte, Javier Alonso
Soria, Ivana
Baumeister, Elsa
Capozzo, Alejandra
author Cardoso, Nancy
author_facet Cardoso, Nancy
Mansilla, Florencia Celeste
Benedetti, Estefanía
Turco, Cecilia Soledad
Barone, Lucas Jose
Iserte, Javier Alonso
Soria, Ivana
Baumeister, Elsa
Capozzo, Alejandra
author_role author
author2 Mansilla, Florencia Celeste
Benedetti, Estefanía
Turco, Cecilia Soledad
Barone, Lucas Jose
Iserte, Javier Alonso
Soria, Ivana
Baumeister, Elsa
Capozzo, Alejandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19
Interferonas
Viricidas
Virus
Interferons
Antiviral Agents
Viruses
In vitro
topic COVID-19
Interferonas
Viricidas
Virus
Interferons
Antiviral Agents
Viruses
In vitro
dc.description.none.fl_txt_mv Interferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2.
Instituto de Virología
Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benedetti, Estefanía. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; Argentina
Fil: Turco Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barone, Lucas Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iserte, Javier Alonso. Fundación Instituto Leloir. Structural Bioinformatics Group; Argentina
Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baumeister, Elsa. Instituto Nacional de Enfermedades Infecciosas, INEI–ANLIS “Dr. Carlos G. Malbrán". Servicio Virosis Respiratorias; Argentina
Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Interferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2.
publishDate 2020
dc.date.none.fl_str_mv 2020-11
2021-01-08T18:28:54Z
2021-01-08T18:28:54Z
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info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fvets.2020.603622/full
http://hdl.handle.net/20.500.12123/8588
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https://doi.org/10.3389/fvets.2020.603622
url https://www.frontiersin.org/articles/10.3389/fvets.2020.603622/full
http://hdl.handle.net/20.500.12123/8588
https://doi.org/10.3389/fvets.2020.603622
identifier_str_mv 2297-1769
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language eng
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
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publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Veterinary Science 7 : 603622 (Noviembre 2020)
reponame:INTA Digital (INTA)
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