Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells

Autores
Rosales, Juan José; Brunner, María Belén; Rodríguez, Marcelo; Marin, Maia Solange; Pérez, Sandra
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
Varicellovirus bovinealpha (BoAHV) types 5 and 1 are closely-related, neurotropic alphaherpesviruses. BoAHV-5 is the etiological agent of non-suppurative meningoencephalitis in calves, whereas BoAHV-1 is responsible for several syndromes in cattle, including respiratory and reproductive diseases. The innate immune response mediated by TLR3 and TLR7 is crucial in controlling infection and modulating pro-inflammatory cytokines, such as IFNs. In this study, it was evaluated whether TLR3 and TLR7 agonists affect BoAHV replication and whether TLR stimulation has an effect on the IFN-λ3 response in neural cells. TLR3 and TLR7 expression in neural cells was induced by the TLR agonists, Poly I:C and Imiquimod, respectively. The antiviral effect of the agonists varied with the virus strain. TLR7 was suppressed early after BoAHV-5 infection and it was upregulated during BoAHV-1 infection. Imiquimod pre-treatment of neural cells induced higher levels of TLR7 mRNA and reduced the replication of the natural BoAHV-5/1 recombinant. In this study, TLR3 expression was completely inhibited during infection with BoAHV-5 and there was a marked up-regulation of TLR3 mRNA during BoAHV-1 infection. Poly I:C treatment up-regulated TLR3 expression in infected cells but a detrimental effect on BoAHV-5 replication was not observed. Infection of neural cells with the recombinant virus A665 stimulated TLR3 expression late in the infectious cycle. Steady levels of BoAHV-1 replication were maintained in the presence of IFN-λ3 and this cytokine was unable to slow the replication of BoAHV-5. For BoAHV-5/1 A663 strain there was a consistent induction of IFN-λ3 throughout the infection period and maximum A663 titers at advanced stages of the replication cycle were in agreement with a decrease in expression levels. The study emphasizes the importance of strain-specific factors, the infection phase and the cell type involved in virus- and agonist-induced TLR and IFN-λ3 expression. Furthermore, these results evidenced that a deeper analysis on the role and activity of TLR agonists on BoAHV infection should be conducted to evaluate their potential as preventive or therapeutic molecules.
EEA Balcarce
Fil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Rosales, Juan José. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Brunner, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Brunner, María Belén. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Marin, Maia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Pérez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Pérez, Sandra. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fuente
Microbial Pathogenesis 202 : 107433 (May 2025)
Materia
Ganado Bovino
Herpes Virus Bovino
Agonista
Sistema Nervioso
Células
Enfermedades de los Animales
Cattle
Bovine Herpesvirus
Agonists
Nervous System
Cells
Animal Diseases
Nivel de accesibilidad
acceso restringido
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:20.500.12123/23006
Acceder
id INTADig_b9646282f3676c395a0f87ab312b19fb
oai_identifier_str oai:localhost:20.500.12123/23006
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cellsRosales, Juan JoséBrunner, María BelénRodríguez, MarceloMarin, Maia SolangePérez, SandraGanado BovinoHerpes Virus BovinoAgonistaSistema NerviosoCélulasEnfermedades de los AnimalesCattleBovine HerpesvirusAgonistsNervous SystemCellsAnimal DiseasesVaricellovirus bovinealpha (BoAHV) types 5 and 1 are closely-related, neurotropic alphaherpesviruses. BoAHV-5 is the etiological agent of non-suppurative meningoencephalitis in calves, whereas BoAHV-1 is responsible for several syndromes in cattle, including respiratory and reproductive diseases. The innate immune response mediated by TLR3 and TLR7 is crucial in controlling infection and modulating pro-inflammatory cytokines, such as IFNs. In this study, it was evaluated whether TLR3 and TLR7 agonists affect BoAHV replication and whether TLR stimulation has an effect on the IFN-λ3 response in neural cells. TLR3 and TLR7 expression in neural cells was induced by the TLR agonists, Poly I:C and Imiquimod, respectively. The antiviral effect of the agonists varied with the virus strain. TLR7 was suppressed early after BoAHV-5 infection and it was upregulated during BoAHV-1 infection. Imiquimod pre-treatment of neural cells induced higher levels of TLR7 mRNA and reduced the replication of the natural BoAHV-5/1 recombinant. In this study, TLR3 expression was completely inhibited during infection with BoAHV-5 and there was a marked up-regulation of TLR3 mRNA during BoAHV-1 infection. Poly I:C treatment up-regulated TLR3 expression in infected cells but a detrimental effect on BoAHV-5 replication was not observed. Infection of neural cells with the recombinant virus A665 stimulated TLR3 expression late in the infectious cycle. Steady levels of BoAHV-1 replication were maintained in the presence of IFN-λ3 and this cytokine was unable to slow the replication of BoAHV-5. For BoAHV-5/1 A663 strain there was a consistent induction of IFN-λ3 throughout the infection period and maximum A663 titers at advanced stages of the replication cycle were in agreement with a decrease in expression levels. The study emphasizes the importance of strain-specific factors, the infection phase and the cell type involved in virus- and agonist-induced TLR and IFN-λ3 expression. Furthermore, these results evidenced that a deeper analysis on the role and activity of TLR agonists on BoAHV infection should be conducted to evaluate their potential as preventive or therapeutic molecules.EEA BalcarceFil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Rosales, Juan José. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Brunner, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Brunner, María Belén. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Marin, Maia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Pérez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Pérez, Sandra. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaElsevierinfo:eu-repo/date/embargoEnd/2026-07-142025-07-14T10:29:34Z2025-07-14T10:29:34Z2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/23006https://www.sciencedirect.com/science/article/abs/pii/S08824010250015851096-1208 (Online)0882-4010 (Print)https://doi.org/10.1016/j.micpath.2025.107433Microbial Pathogenesis 202 : 107433 (May 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-04T09:51:10Zoai:localhost:20.500.12123/23006instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:51:11.067INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
title Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
spellingShingle Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
Rosales, Juan José
Ganado Bovino
Herpes Virus Bovino
Agonista
Sistema Nervioso
Células
Enfermedades de los Animales
Cattle
Bovine Herpesvirus
Agonists
Nervous System
Cells
Animal Diseases
title_short Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
title_full Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
title_fullStr Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
title_full_unstemmed Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
title_sort Varicellovirus bovinealpha (BoAHV) 1 and 5 activate distinct toll-like receptors signaling pathways in neural cells
dc.creator.none.fl_str_mv Rosales, Juan José
Brunner, María Belén
Rodríguez, Marcelo
Marin, Maia Solange
Pérez, Sandra
author Rosales, Juan José
author_facet Rosales, Juan José
Brunner, María Belén
Rodríguez, Marcelo
Marin, Maia Solange
Pérez, Sandra
author_role author
author2 Brunner, María Belén
Rodríguez, Marcelo
Marin, Maia Solange
Pérez, Sandra
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ganado Bovino
Herpes Virus Bovino
Agonista
Sistema Nervioso
Células
Enfermedades de los Animales
Cattle
Bovine Herpesvirus
Agonists
Nervous System
Cells
Animal Diseases
topic Ganado Bovino
Herpes Virus Bovino
Agonista
Sistema Nervioso
Células
Enfermedades de los Animales
Cattle
Bovine Herpesvirus
Agonists
Nervous System
Cells
Animal Diseases
dc.description.none.fl_txt_mv Varicellovirus bovinealpha (BoAHV) types 5 and 1 are closely-related, neurotropic alphaherpesviruses. BoAHV-5 is the etiological agent of non-suppurative meningoencephalitis in calves, whereas BoAHV-1 is responsible for several syndromes in cattle, including respiratory and reproductive diseases. The innate immune response mediated by TLR3 and TLR7 is crucial in controlling infection and modulating pro-inflammatory cytokines, such as IFNs. In this study, it was evaluated whether TLR3 and TLR7 agonists affect BoAHV replication and whether TLR stimulation has an effect on the IFN-λ3 response in neural cells. TLR3 and TLR7 expression in neural cells was induced by the TLR agonists, Poly I:C and Imiquimod, respectively. The antiviral effect of the agonists varied with the virus strain. TLR7 was suppressed early after BoAHV-5 infection and it was upregulated during BoAHV-1 infection. Imiquimod pre-treatment of neural cells induced higher levels of TLR7 mRNA and reduced the replication of the natural BoAHV-5/1 recombinant. In this study, TLR3 expression was completely inhibited during infection with BoAHV-5 and there was a marked up-regulation of TLR3 mRNA during BoAHV-1 infection. Poly I:C treatment up-regulated TLR3 expression in infected cells but a detrimental effect on BoAHV-5 replication was not observed. Infection of neural cells with the recombinant virus A665 stimulated TLR3 expression late in the infectious cycle. Steady levels of BoAHV-1 replication were maintained in the presence of IFN-λ3 and this cytokine was unable to slow the replication of BoAHV-5. For BoAHV-5/1 A663 strain there was a consistent induction of IFN-λ3 throughout the infection period and maximum A663 titers at advanced stages of the replication cycle were in agreement with a decrease in expression levels. The study emphasizes the importance of strain-specific factors, the infection phase and the cell type involved in virus- and agonist-induced TLR and IFN-λ3 expression. Furthermore, these results evidenced that a deeper analysis on the role and activity of TLR agonists on BoAHV infection should be conducted to evaluate their potential as preventive or therapeutic molecules.
EEA Balcarce
Fil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Rosales, Juan José. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Brunner, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Brunner, María Belén. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Marin, Maia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Pérez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Pérez, Sandra. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
description Varicellovirus bovinealpha (BoAHV) types 5 and 1 are closely-related, neurotropic alphaherpesviruses. BoAHV-5 is the etiological agent of non-suppurative meningoencephalitis in calves, whereas BoAHV-1 is responsible for several syndromes in cattle, including respiratory and reproductive diseases. The innate immune response mediated by TLR3 and TLR7 is crucial in controlling infection and modulating pro-inflammatory cytokines, such as IFNs. In this study, it was evaluated whether TLR3 and TLR7 agonists affect BoAHV replication and whether TLR stimulation has an effect on the IFN-λ3 response in neural cells. TLR3 and TLR7 expression in neural cells was induced by the TLR agonists, Poly I:C and Imiquimod, respectively. The antiviral effect of the agonists varied with the virus strain. TLR7 was suppressed early after BoAHV-5 infection and it was upregulated during BoAHV-1 infection. Imiquimod pre-treatment of neural cells induced higher levels of TLR7 mRNA and reduced the replication of the natural BoAHV-5/1 recombinant. In this study, TLR3 expression was completely inhibited during infection with BoAHV-5 and there was a marked up-regulation of TLR3 mRNA during BoAHV-1 infection. Poly I:C treatment up-regulated TLR3 expression in infected cells but a detrimental effect on BoAHV-5 replication was not observed. Infection of neural cells with the recombinant virus A665 stimulated TLR3 expression late in the infectious cycle. Steady levels of BoAHV-1 replication were maintained in the presence of IFN-λ3 and this cytokine was unable to slow the replication of BoAHV-5. For BoAHV-5/1 A663 strain there was a consistent induction of IFN-λ3 throughout the infection period and maximum A663 titers at advanced stages of the replication cycle were in agreement with a decrease in expression levels. The study emphasizes the importance of strain-specific factors, the infection phase and the cell type involved in virus- and agonist-induced TLR and IFN-λ3 expression. Furthermore, these results evidenced that a deeper analysis on the role and activity of TLR agonists on BoAHV infection should be conducted to evaluate their potential as preventive or therapeutic molecules.
publishDate 2025
dc.date.none.fl_str_mv 2025-07-14T10:29:34Z
2025-07-14T10:29:34Z
2025-05
info:eu-repo/date/embargoEnd/2026-07-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/23006
https://www.sciencedirect.com/science/article/abs/pii/S0882401025001585
1096-1208 (Online)
0882-4010 (Print)
https://doi.org/10.1016/j.micpath.2025.107433
url http://hdl.handle.net/20.500.12123/23006
https://www.sciencedirect.com/science/article/abs/pii/S0882401025001585
https://doi.org/10.1016/j.micpath.2025.107433
identifier_str_mv 1096-1208 (Online)
0882-4010 (Print)
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
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 restrictedAccess
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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Microbial Pathogenesis 202 : 107433 (May 2025)
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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