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Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs

Under experimental conditions, pigs infected with Ebola Virus (EBOV) develop disease and can readily transmit the virus to non-human primates or pigs. In the event of accidental or intentional EBOV infection of domestic pigs, complex and time-consuming safe depopulation and carcass disposal are expe...

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Autores principales: Senthilkumaran, Chandrika, Kroeker, Andrea L., Smith, Gregory, Embury-Hyatt, Carissa, Collignon, Brad, Ramirez-Medina, Elizabeth, Azzinaro, Paul A., Pickering, Bradley S., Diaz-San Segundo, Fayna, Weingartl, Hana M., de los Santos, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031749/
https://www.ncbi.nlm.nih.gov/pubmed/35456124
http://dx.doi.org/10.3390/pathogens11040449
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author Senthilkumaran, Chandrika
Kroeker, Andrea L.
Smith, Gregory
Embury-Hyatt, Carissa
Collignon, Brad
Ramirez-Medina, Elizabeth
Azzinaro, Paul A.
Pickering, Bradley S.
Diaz-San Segundo, Fayna
Weingartl, Hana M.
de los Santos, Teresa
author_facet Senthilkumaran, Chandrika
Kroeker, Andrea L.
Smith, Gregory
Embury-Hyatt, Carissa
Collignon, Brad
Ramirez-Medina, Elizabeth
Azzinaro, Paul A.
Pickering, Bradley S.
Diaz-San Segundo, Fayna
Weingartl, Hana M.
de los Santos, Teresa
author_sort Senthilkumaran, Chandrika
collection PubMed
description Under experimental conditions, pigs infected with Ebola Virus (EBOV) develop disease and can readily transmit the virus to non-human primates or pigs. In the event of accidental or intentional EBOV infection of domestic pigs, complex and time-consuming safe depopulation and carcass disposal are expected. Delaying or preventing transmission through a reduction in viral shedding is an absolute necessity to limit the spread of the virus. In this study, we tested whether porcine interferon-α or λ3 (porIFNα or porIFNλ3) delivered by a replication-defective human type 5 adenovirus vector (Ad5-porIFNα or Ad5-porIFNλ3) could limit EBOV replication and shedding in domestic pigs. Our results show that pigs pre-treated with Ad5-porIFNα did not develop measurable clinical signs, did not shed virus RNA, and displayed strongly reduced viral RNA load in tissues. A microarray analysis of peripheral blood mononuclear cells indicated that Ad5-porIFNα treatment led to clear upregulation in immune and inflammatory responses probably involved in protection against disease. Our results indicate that administration of Ad5-porIFNα can potentially be used to limit the spread of EBOV in pigs.
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spelling pubmed-90317492022-04-23 Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs Senthilkumaran, Chandrika Kroeker, Andrea L. Smith, Gregory Embury-Hyatt, Carissa Collignon, Brad Ramirez-Medina, Elizabeth Azzinaro, Paul A. Pickering, Bradley S. Diaz-San Segundo, Fayna Weingartl, Hana M. de los Santos, Teresa Pathogens Article Under experimental conditions, pigs infected with Ebola Virus (EBOV) develop disease and can readily transmit the virus to non-human primates or pigs. In the event of accidental or intentional EBOV infection of domestic pigs, complex and time-consuming safe depopulation and carcass disposal are expected. Delaying or preventing transmission through a reduction in viral shedding is an absolute necessity to limit the spread of the virus. In this study, we tested whether porcine interferon-α or λ3 (porIFNα or porIFNλ3) delivered by a replication-defective human type 5 adenovirus vector (Ad5-porIFNα or Ad5-porIFNλ3) could limit EBOV replication and shedding in domestic pigs. Our results show that pigs pre-treated with Ad5-porIFNα did not develop measurable clinical signs, did not shed virus RNA, and displayed strongly reduced viral RNA load in tissues. A microarray analysis of peripheral blood mononuclear cells indicated that Ad5-porIFNα treatment led to clear upregulation in immune and inflammatory responses probably involved in protection against disease. Our results indicate that administration of Ad5-porIFNα can potentially be used to limit the spread of EBOV in pigs. MDPI 2022-04-08 /pmc/articles/PMC9031749/ /pubmed/35456124 http://dx.doi.org/10.3390/pathogens11040449 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Senthilkumaran, Chandrika
Kroeker, Andrea L.
Smith, Gregory
Embury-Hyatt, Carissa
Collignon, Brad
Ramirez-Medina, Elizabeth
Azzinaro, Paul A.
Pickering, Bradley S.
Diaz-San Segundo, Fayna
Weingartl, Hana M.
de los Santos, Teresa
Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title_full Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title_fullStr Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title_full_unstemmed Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title_short Treatment with Ad5-Porcine Interferon-α Attenuates Ebolavirus Disease in Pigs
title_sort treatment with ad5-porcine interferon-α attenuates ebolavirus disease in pigs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031749/
https://www.ncbi.nlm.nih.gov/pubmed/35456124
http://dx.doi.org/10.3390/pathogens11040449
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