TY - JOUR
T1 - Transcriptomic analysis of persistent infection with foot-And-mouth disease virus in cattle suggests impairment of apoptosis and cell-mediated immunity in the nasopharynx
AU - Eschbaumer, Michael
AU - Stenfeldt, Carolina
AU - Smoliga, George R.
AU - Pacheco, Juan M.
AU - Rodriguez, Luis L.
AU - Li, Robert W.
AU - Zhu, James
AU - Arzt, Jonathan
N1 - Publisher Copyright:
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2016/9
Y1 - 2016/9
N2 - In order to investigate the mechanisms of persistent foot-And-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-Transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinantFMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carrierswere furthercompared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers.Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandinE2 production and the induction of regulatoryT cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-Apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairmentof apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatoryT cells.
AB - In order to investigate the mechanisms of persistent foot-And-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-Transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinantFMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carrierswere furthercompared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers.Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandinE2 production and the induction of regulatoryT cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-Apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairmentof apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatoryT cells.
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U2 - 10.1371/journal.pone.0162750
DO - 10.1371/journal.pone.0162750
M3 - Article
C2 - 27643611
AN - SCOPUS:84992323024
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 9
M1 - e0162750
ER -