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Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytes secrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT) pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studied the histopathology and dyna...

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Autores principales: Marín-López, Alejandro, Bermúdez, Roberto, Calvo-Pinilla, Eva, Moreno, Sandra, Brun, Alejandro, Ortego, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166487/
https://www.ncbi.nlm.nih.gov/pubmed/27994510
http://dx.doi.org/10.7150/ijbs.14967
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author Marín-López, Alejandro
Bermúdez, Roberto
Calvo-Pinilla, Eva
Moreno, Sandra
Brun, Alejandro
Ortego, Javier
author_facet Marín-López, Alejandro
Bermúdez, Roberto
Calvo-Pinilla, Eva
Moreno, Sandra
Brun, Alejandro
Ortego, Javier
author_sort Marín-López, Alejandro
collection PubMed
description Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytes secrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT) pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studied the histopathology and dynamics of leukocyte populations in different target tissues (spleen, thymus, and lung) during BTV-4 infection by histological and immunohistochemical techniques. The spleen and thymus of BTV-4 infected mice showed severe lymphoid depletion on H&E stained sections. This finding was confirmed by IHC, showing moderate decreased immunopositivity against CD3 in the thymus, and scarce immunoreactivity against CD3 and CD79 in the rest of the white pulp in the spleen, together with an increase in MAC387 immunostaining. BTV-4 infection also induced the expression of active caspase-3 in the spleen, where apoptotic debris was observed by H&E. A dramatic increase in iNOS immunoreactivity associated to necrotic areas of the white pulp was observed, being less noticeable in the thymus and the lung. The induction of pro-inflammatory cytokines in tissues where BTV replicates was evaluated by measuring transcript levels by RT-qPCR. BTV-4 infection led to enhance transcription of IFN-γ, TNF, IL-6, IL-12-p40, and IL-1β mRNA in the thymus, spleen and lung, correlating with the level of virus replication in these tissues. Disease progression and pathogenesis in IFNAR(-/-) mice closely mimics hallmarks of bluetongue disease in ruminants. IFNAR(-/-) mice are a good choice to facilitate a faster advance in the field of orbiviruses.
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spelling pubmed-51664872016-12-19 Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4 Marín-López, Alejandro Bermúdez, Roberto Calvo-Pinilla, Eva Moreno, Sandra Brun, Alejandro Ortego, Javier Int J Biol Sci Research Paper Bluetongue virus (BTV) replicates in lymphoid tissues where infected mononuclear leukocytes secrete proinflammatory and vasoactive mediators that can contribute to bluetongue (BT) pathogenesis. Using the well-characterized IFNAR(-/-) mice animal model, we have now studied the histopathology and dynamics of leukocyte populations in different target tissues (spleen, thymus, and lung) during BTV-4 infection by histological and immunohistochemical techniques. The spleen and thymus of BTV-4 infected mice showed severe lymphoid depletion on H&E stained sections. This finding was confirmed by IHC, showing moderate decreased immunopositivity against CD3 in the thymus, and scarce immunoreactivity against CD3 and CD79 in the rest of the white pulp in the spleen, together with an increase in MAC387 immunostaining. BTV-4 infection also induced the expression of active caspase-3 in the spleen, where apoptotic debris was observed by H&E. A dramatic increase in iNOS immunoreactivity associated to necrotic areas of the white pulp was observed, being less noticeable in the thymus and the lung. The induction of pro-inflammatory cytokines in tissues where BTV replicates was evaluated by measuring transcript levels by RT-qPCR. BTV-4 infection led to enhance transcription of IFN-γ, TNF, IL-6, IL-12-p40, and IL-1β mRNA in the thymus, spleen and lung, correlating with the level of virus replication in these tissues. Disease progression and pathogenesis in IFNAR(-/-) mice closely mimics hallmarks of bluetongue disease in ruminants. IFNAR(-/-) mice are a good choice to facilitate a faster advance in the field of orbiviruses. Ivyspring International Publisher 2016-11-24 /pmc/articles/PMC5166487/ /pubmed/27994510 http://dx.doi.org/10.7150/ijbs.14967 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Marín-López, Alejandro
Bermúdez, Roberto
Calvo-Pinilla, Eva
Moreno, Sandra
Brun, Alejandro
Ortego, Javier
Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title_full Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title_fullStr Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title_full_unstemmed Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title_short Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4
title_sort pathological characterization of ifnar(-/-) mice infected with bluetongue virus serotype 4
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166487/
https://www.ncbi.nlm.nih.gov/pubmed/27994510
http://dx.doi.org/10.7150/ijbs.14967
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