Dataset Information

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.

SUBMITTER: Eschbaumer M

PROVIDER: S-EPMC5028045 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Eschbaumer Michael M Stenfeldt Carolina C Smoliga George R GR Pacheco Juan M JM Rodriguez Luis L LL Li Robert W RW Zhu James J Arzt Jonathan J

PloS one 20160919 9

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 pe ...[more]

PMID: 27643611

Similar Datasets

Project description:A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicle-associated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+/MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+/CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of epithelial cells of the nasopharyngeal mucosa that could enable shedding and long-term persistence of infectious virus. Additionally, these data indicate different mechanisms within the immediate host response to infection between non-vaccinated and vaccinated cattle.

Project description:Nigeria is a large densely populated country in West Africa. Most of its livestock is raised in a pastoralist production system with typical long distance migration in search of water and feed. As the demand for animal products largely exceeds the domestic production, large numbers of livestock are imported from neighboring countries without sanitary restrictions. In Nigeria, foot-and-mouth disease virus (FMDV) serotypes O, A, and Southern African Territories (SAT)2 are endemic for a long time. Clinical outbreaks of FMD due to serotype SAT1 are described again since 2015, after an absence of more than 30 years. Historically, outbreaks of FMD due to serotypes O, A, SAT1, and SAT2 were each time associated with trade of cattle entering Nigeria from neighboring countries. In the present study, tissue samples from 27 outbreaks of FMD were collected in Nigerian cattle from 2012 until 2017 in six different States and in the Federal Capital Territory. FMDV was isolated and serotyped and further characterized by VP1 sequencing and phylogenetic analysis to gain more knowledge on FMDV circulation in Nigeria. Half of the outbreaks were characterized as FMDV topotype O/EA-3, while outbreaks with other serotypes and topotypes were-in descending order-less prevalent: A/Africa/G-IV, SAT1/X, SAT2/VII, and O/WA. The high dynamics and omnipresence of FMD in Nigeria were illustrated in Plateau State where FMDV serotypes O, SAT1, and SAT2 were isolated during the course of the study, while at some point in the study, outbreaks due to FMDV serotype A were observed in three remote States. The genetic and phylogenetic analysis suggests a mixed origin of FMD outbreaks. Some outbreaks seem to be caused by sustained local transmission of FMDV strains present in Nigeria since a number of years, while other outbreaks seem to be related to recent incursions with new FMDV strains. The role of African buffaloes in the etiology of FMD in Nigeria is unclear, and sampling of wildlife is needed. The results of the present study suggest that systematic sample collection is essential to understand the complex concomitance of FMDV strains in Nigeria and essential to support the implementation of a vaccination-based control plan.

Project description:The objective of the current study was to update parameterization of mathematical simulation models for foot-and-mouth disease (FMD) spread in cattle utilizing recent knowledge of FMD virus (FMDV) pathogenesis and infection dynamics to estimate the duration of distinct phases of FMD. Specifically, the durations of incubation, latent, and infectious periods were estimated for 3 serotypes (O, Asia1, and A) of FMDV, individually and collectively (pan-serotypic). Animal-level data were used in Accelerated Failure Time (AFT) models to estimate the duration of the defined phases of infection, while also investigating the influence of factors related to the experimental design (exposure methods) and virus serotype on disease progression. Substantial influences upon the estimated duration of distinct phases of FMD included the quantity of viral shedding used as a proxy for the onset of infectiousness, virus serotypes, and experimental exposure methods. The use of detection of any viral RNA in nasal secretions as a proxy of infectiousness lengthened the total infectious period compared to use of threshold-based detection. Additionally, the experimental system used to infect the animals also had significant effects on the duration of distinct phases of disease. Overall, the mean [95% Confidence Interval (CI)] durations of pan-serotype disease phases in cattle were estimated to be: incubation phase = 3.6 days (2.7-4.8), latent phase = 1.5 days (1.1-2.1), subclinical infectious phase = 2.2 days (1.5-3.5), clinical infectious phase = 8.5 days (6.2-11.6), and total infectious phase = 10.8 days (8.2-14.2). This study highlights the importance of identifying appropriate proxy measures to define the onset and duration of infectiousness in FMDV-infected cattle in the absence of actual transmission data. Additionally, it is demonstrated herein that factors associated with experimental design, such as virus exposure methods, may significantly affect disease progression in individual animals and should be considered when data is extrapolated from experimental studies. Given limitations in experimental data availability, pan-serotypic parameters which include all routes of exposure and a threshold-defined onset of infectiousness may be the most robust parameters for exploratory disease spread modeling approaches, when information on the specific virus of interest is not available.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets