TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells

Autores
Brunner, Maria Belen; Rosales, Juan José; Ladera Gomez, Marla Eliana; Nieto Farías, María Victoria; Verna, Andrea Elizabeth; Perez, Sandra
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Varicellovirus bovinealpha (BoAHV) 1 and 5 are alphaherpesviruses that differ in their neuropathogenic potential. While BoAHV-5 causes necrotizing meningoencephalitis in calves, neurological cases associated with BoAHV-1 are less frequent. In this study we used differentiated the human neuroblastoma cell line (SH-SY5Y) to evaluate the mRNA expression of Toll-like receptor 3 (TLR3), its adaptor molecule TRIF and the production of interferons and pro-inflammatory cytokines during infection with both alphaherpesviruses. TLR3 was activated with polyinosinic acid: polycytidylic acid (Poly I:C) and it was genetically silenced using TLR3-targeted siRNA. BoAHV infection induced an initial upregulation of TLR3, followed by a notable decrease, particularly in BoAHV-5-infected cells. TLR3 knockdown was effective for 72 h in uninfected cells although it was reversed shortly after BoAHV infection. In the presence of activated TLR3, virus titers remained high, indicating limited antiviral activity of TLR3 signaling. TRIF was downregulated early after infection, implying viral interference with the innate immune response. In contrast, Poly I:C upregulated TLR3 and TRIF. IFN-β was upregulated following infection and IFN-α/β, TNF-α and IL-6 were induced even in TLR3-silenced cells, implicating the involvement of alternative signaling pathways. These findings demonstrate how bovine alphaherpesviruses modulate the innate immune mechanisms, highlighting differential viral strategies to evade the immune response which may contribute to neuropathogenesis.
Fil: Brunner, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Ladera Gomez, Marla Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Nieto Farías, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Verna, Andrea Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Perez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Materia
BoAHV
neuropathogenic potential
TLR3
qPCR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/272480
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/272480
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cellsBrunner, Maria BelenRosales, Juan JoséLadera Gomez, Marla ElianaNieto Farías, María VictoriaVerna, Andrea ElizabethPerez, SandraBoAHVneuropathogenic potentialTLR3qPCRhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Varicellovirus bovinealpha (BoAHV) 1 and 5 are alphaherpesviruses that differ in their neuropathogenic potential. While BoAHV-5 causes necrotizing meningoencephalitis in calves, neurological cases associated with BoAHV-1 are less frequent. In this study we used differentiated the human neuroblastoma cell line (SH-SY5Y) to evaluate the mRNA expression of Toll-like receptor 3 (TLR3), its adaptor molecule TRIF and the production of interferons and pro-inflammatory cytokines during infection with both alphaherpesviruses. TLR3 was activated with polyinosinic acid: polycytidylic acid (Poly I:C) and it was genetically silenced using TLR3-targeted siRNA. BoAHV infection induced an initial upregulation of TLR3, followed by a notable decrease, particularly in BoAHV-5-infected cells. TLR3 knockdown was effective for 72 h in uninfected cells although it was reversed shortly after BoAHV infection. In the presence of activated TLR3, virus titers remained high, indicating limited antiviral activity of TLR3 signaling. TRIF was downregulated early after infection, implying viral interference with the innate immune response. In contrast, Poly I:C upregulated TLR3 and TRIF. IFN-β was upregulated following infection and IFN-α/β, TNF-α and IL-6 were induced even in TLR3-silenced cells, implicating the involvement of alternative signaling pathways. These findings demonstrate how bovine alphaherpesviruses modulate the innate immune mechanisms, highlighting differential viral strategies to evade the immune response which may contribute to neuropathogenesis.Fil: Brunner, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Ladera Gomez, Marla Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Nieto Farías, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Verna, Andrea Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Perez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaElsevier Science2025-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/272480Brunner, Maria Belen; Rosales, Juan José; Ladera Gomez, Marla Eliana; Nieto Farías, María Victoria; Verna, Andrea Elizabeth; et al.; TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells; Elsevier Science; Microbes and Infection; 105558; 8-2025; 1-291286-4579CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/40782939/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.micinf.2025.105558info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1286457925000905info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:02:58Zoai:ri.conicet.gov.ar:11336/272480instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:02:58.578CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
title TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
spellingShingle TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
Brunner, Maria Belen
BoAHV
neuropathogenic potential
TLR3
qPCR
title_short TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
title_full TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
title_fullStr TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
title_full_unstemmed TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
title_sort TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells
dc.creator.none.fl_str_mv Brunner, Maria Belen
Rosales, Juan José
Ladera Gomez, Marla Eliana
Nieto Farías, María Victoria
Verna, Andrea Elizabeth
Perez, Sandra
author Brunner, Maria Belen
author_facet Brunner, Maria Belen
Rosales, Juan José
Ladera Gomez, Marla Eliana
Nieto Farías, María Victoria
Verna, Andrea Elizabeth
Perez, Sandra
author_role author
author2 Rosales, Juan José
Ladera Gomez, Marla Eliana
Nieto Farías, María Victoria
Verna, Andrea Elizabeth
Perez, Sandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BoAHV
neuropathogenic potential
TLR3
qPCR
topic BoAHV
neuropathogenic potential
TLR3
qPCR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Varicellovirus bovinealpha (BoAHV) 1 and 5 are alphaherpesviruses that differ in their neuropathogenic potential. While BoAHV-5 causes necrotizing meningoencephalitis in calves, neurological cases associated with BoAHV-1 are less frequent. In this study we used differentiated the human neuroblastoma cell line (SH-SY5Y) to evaluate the mRNA expression of Toll-like receptor 3 (TLR3), its adaptor molecule TRIF and the production of interferons and pro-inflammatory cytokines during infection with both alphaherpesviruses. TLR3 was activated with polyinosinic acid: polycytidylic acid (Poly I:C) and it was genetically silenced using TLR3-targeted siRNA. BoAHV infection induced an initial upregulation of TLR3, followed by a notable decrease, particularly in BoAHV-5-infected cells. TLR3 knockdown was effective for 72 h in uninfected cells although it was reversed shortly after BoAHV infection. In the presence of activated TLR3, virus titers remained high, indicating limited antiviral activity of TLR3 signaling. TRIF was downregulated early after infection, implying viral interference with the innate immune response. In contrast, Poly I:C upregulated TLR3 and TRIF. IFN-β was upregulated following infection and IFN-α/β, TNF-α and IL-6 were induced even in TLR3-silenced cells, implicating the involvement of alternative signaling pathways. These findings demonstrate how bovine alphaherpesviruses modulate the innate immune mechanisms, highlighting differential viral strategies to evade the immune response which may contribute to neuropathogenesis.
Fil: Brunner, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Rosales, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Ladera Gomez, Marla Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Nieto Farías, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Verna, Andrea Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Perez, Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
description Varicellovirus bovinealpha (BoAHV) 1 and 5 are alphaherpesviruses that differ in their neuropathogenic potential. While BoAHV-5 causes necrotizing meningoencephalitis in calves, neurological cases associated with BoAHV-1 are less frequent. In this study we used differentiated the human neuroblastoma cell line (SH-SY5Y) to evaluate the mRNA expression of Toll-like receptor 3 (TLR3), its adaptor molecule TRIF and the production of interferons and pro-inflammatory cytokines during infection with both alphaherpesviruses. TLR3 was activated with polyinosinic acid: polycytidylic acid (Poly I:C) and it was genetically silenced using TLR3-targeted siRNA. BoAHV infection induced an initial upregulation of TLR3, followed by a notable decrease, particularly in BoAHV-5-infected cells. TLR3 knockdown was effective for 72 h in uninfected cells although it was reversed shortly after BoAHV infection. In the presence of activated TLR3, virus titers remained high, indicating limited antiviral activity of TLR3 signaling. TRIF was downregulated early after infection, implying viral interference with the innate immune response. In contrast, Poly I:C upregulated TLR3 and TRIF. IFN-β was upregulated following infection and IFN-α/β, TNF-α and IL-6 were induced even in TLR3-silenced cells, implicating the involvement of alternative signaling pathways. These findings demonstrate how bovine alphaherpesviruses modulate the innate immune mechanisms, highlighting differential viral strategies to evade the immune response which may contribute to neuropathogenesis.
publishDate 2025
dc.date.none.fl_str_mv 2025-08
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/11336/272480
Brunner, Maria Belen; Rosales, Juan José; Ladera Gomez, Marla Eliana; Nieto Farías, María Victoria; Verna, Andrea Elizabeth; et al.; TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells; Elsevier Science; Microbes and Infection; 105558; 8-2025; 1-29
1286-4579
CONICET Digital
CONICET
url http://hdl.handle.net/11336/272480
identifier_str_mv Brunner, Maria Belen; Rosales, Juan José; Ladera Gomez, Marla Eliana; Nieto Farías, María Victoria; Verna, Andrea Elizabeth; et al.; TLR3 regulation and cytokine response during BoAHV-1 and BoAHV-5 infection of neuronal-like cells; Elsevier Science; Microbes and Infection; 105558; 8-2025; 1-29
1286-4579
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/40782939/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.micinf.2025.105558
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1286457925000905
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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