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.
abstract: 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-carriers were further compared 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 prostaglandin E2 production and the induction of regulatory T 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 impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.|Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN, United States of America.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-1104-0695
authors.initials: M
authors.lastname: Eschbaumer
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.|Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN, United States of America.
authors.forename: Carolina
authors.initials: C
authors.lastname: Stenfeldt
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.
authors.forename: George R
authors.initials: GR
authors.lastname: Smoliga
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pacheco
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.
authors.forename: Luis L
authors.initials: LL
authors.lastname: Rodriguez
authors.affiliation: Animal Genomics and Improvement Laboratory (AGIL), USDA-ARS, Beltsville, MD, United States of America.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Li
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Plum Island Animal Disease Center (PIADC), Foreign Animal Disease Research Unit (FADRU), United States Department of Agriculture (USDA)-Agricultural Research Service (ARS), Greenport, NY, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Arzt
mesh_terms: D000818:Animals; D017209:Apoptosis; D002417:Cattle / Q000235:genetics / Q000276:immunology / Q000821:virology*; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D005536:Foot-and-Mouth Disease / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D020869:Gene Expression Profiling; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007113:Immunity, Innate; D009305:Nasopharynx / Q000276:immunology / Q000378:metabolism / Q000821:virology; D059467:Transcriptome; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D014614:Vaccines, Synthetic; D014765:Viral Vaccines