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Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity

We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (...

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Autores principales: Ciccone, Nick A., Smith, Lorraine P., Mwangi, William, Boyd, Amy, Broadbent, Andrew J., Smith, Adrian L., Nair, Venugopal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421744/
https://www.ncbi.nlm.nih.gov/pubmed/28322935
http://dx.doi.org/10.1016/j.dci.2017.03.014
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author Ciccone, Nick A.
Smith, Lorraine P.
Mwangi, William
Boyd, Amy
Broadbent, Andrew J.
Smith, Adrian L.
Nair, Venugopal
author_facet Ciccone, Nick A.
Smith, Lorraine P.
Mwangi, William
Boyd, Amy
Broadbent, Andrew J.
Smith, Adrian L.
Nair, Venugopal
author_sort Ciccone, Nick A.
collection PubMed
description We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS. Such changes correlate with genomic fragmentation and the presence of IBDV capsid protein, VP2. To explore the effects of CD40L, the immature B cell line, DT40, was exposed to recombinant chicken CD40L that resulted in changes in nuclear 5hmC distribution. Collectively, our observations suggest that T cell infiltration exacerbates early immunopathology within the BF during an IBDV infection contributing to B cell genomic instability and death to facilitate viral egress and immunosuppression.
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spelling pubmed-54217442017-08-01 Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity Ciccone, Nick A. Smith, Lorraine P. Mwangi, William Boyd, Amy Broadbent, Andrew J. Smith, Adrian L. Nair, Venugopal Dev Comp Immunol Article We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS. Such changes correlate with genomic fragmentation and the presence of IBDV capsid protein, VP2. To explore the effects of CD40L, the immature B cell line, DT40, was exposed to recombinant chicken CD40L that resulted in changes in nuclear 5hmC distribution. Collectively, our observations suggest that T cell infiltration exacerbates early immunopathology within the BF during an IBDV infection contributing to B cell genomic instability and death to facilitate viral egress and immunosuppression. Elsevier Science 2017-08 /pmc/articles/PMC5421744/ /pubmed/28322935 http://dx.doi.org/10.1016/j.dci.2017.03.014 Text en Crown Copyright © 2017 Published by Elsevier Ltd. All rights reserved. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ciccone, Nick A.
Smith, Lorraine P.
Mwangi, William
Boyd, Amy
Broadbent, Andrew J.
Smith, Adrian L.
Nair, Venugopal
Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title_full Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title_fullStr Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title_full_unstemmed Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title_short Early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in B cell genomic methylation and loss of genome integrity
title_sort early pathogenesis during infectious bursal disease in susceptible chickens is associated with changes in b cell genomic methylation and loss of genome integrity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421744/
https://www.ncbi.nlm.nih.gov/pubmed/28322935
http://dx.doi.org/10.1016/j.dci.2017.03.014
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