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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

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 A 24 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 E 2 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 andmore » 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.« less
Authors:
ORCiD logo [1] ;  [2] ;  [3] ;  [3] ;  [3] ;  [4] ;  [3] ;  [3] ;  [5]
  1. United States Dept. of Agriculture (USDA) - Agricultural Research Service (ARS), Greenport, NY (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States); Friedrich-Loeffler-Institut, Greifswald-Insel Riems (Germany)
  2. United States Dept. of Agriculture (USDA) - Agricultural Research Service (ARS), Greenport, NY (United States); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
  3. United States Dept. of Agriculture (USDA) - Agricultural Research Service (ARS), Greenport, NY (United States)
  4. USDA-ARS, Beltsville, MD (United States)
  5. Univ. of Minnesota College of Veterinary Medicine, Falcon Heights, MN (United States)
Publication Date:
Grant/Contract Number:
1940-32000-057-00D; HSHQPM-13-X-00131
Type:
Published Article
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Research Org:
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 Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
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
OSTI Identifier:
1337794
Alternate Identifier(s):
OSTI ID: 1377844