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Title: Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx

Journal Article · · PLoS ONE
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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 recombinant FMDV 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 further compared to 2 naive 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 over represented. 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 prostaglandin E2 production and the induction of regulatoryT cells were over expressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Furthermore, 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 impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatoryT cells.

Research Organization:
USDA, Agricultural Research Service, Greenport, NY (United States); Science and Technology Directorate of the U.S. Department of Homeland Security, Washington, D.C. (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
1940-32000-057-00D; HSHQPM-13-X-00131
OSTI ID:
1337794
Alternate ID(s):
OSTI ID: 1377844
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Vol. 11 Journal Issue: 9; ISSN 1932-6203
Publisher:
Public Library of Science (PLoS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
T cells
apoptosis
gene expression
regulatory T cells
viral persistence and latency
foot and mouth disease
cattle