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Mechanisms of Tissue Susceptibility to FMDV Persistent Infection Based on Genes Differentially Expressed between Target and Non-target Tissues

ABSTRACT: Comparison of the transcriptiomic profiles using DNA microarray analysis betwween the pharyneal (target of FMDV acute and persistent infection) and lung (target of FMDV acute infection) tissues of cattle

ORGANISM(S): Bos taurus

PROVIDER: GSE232440 | GEO | 2023/09/01

REPOSITORIES: GEO

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Transcriptomic analysis genes involved in the establishment and maintenance of FMDV persistent infection

Project description:In FMDV persistent infection cell lines, we found that many FMDV-free cells (BHK_VEC) occupied. The BHK_VEC cells exhibited resisted to the parental FMDV, and could re-establish a persistent infection when infected with FMDV-OP, revealing a fact that host cells evolved during the persistent infection. To further explore the underlying molecular mechanism, transcriptomic analyses of BHK_VEC, BHK21 and BHK-Op cells were performed by using RNA-seq

2018-03-22 | GSE93045 | GEO

Proteogenomics uncovers critical elements of host response in bovine soft palate epithelial cells following in vitro infection with foot-and-mouth disease virus (FMDV)

Project description:: Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates of up to 100% in cattle. Even after recovery, over 50% of cattle remain subclinically infected and infectious virus can be recovered from the nasopharynx. The pathogen and host factors that contribute to FMDV persistence are currently not understood. Using for the first time primary bovine soft palate multilayers in combination with proteogenomics, we analyzed the transcriptional responses during acute and persistent FMDV infection. During the acute phase viral RNA and protein was detectable in large quantities and in response hundreds of interferon-stimulated genes (ISG) were overexpressed, mediating antiviral activity and apoptosis. Although the number of pro-apoptotic ISGs and the extent of their regulation decreased during persistence, some ISGs with antiviral activity were still highly expressed at that stage. This indicates a long-lasting but ultimately ineffective stimulation of ISGs during FMDV persistence. Furthermore, downregulation of relevant genes suggests an interference with the extracellular matrix that may contribute to the skewed virus-host equilibrium in soft palate epithelial cells.

2019-01-17 | PXD012242 | Pride

Proteogenomics uncovers critical elements of host response in bovine soft palate epithelial cells following in vitro infection with foot-and-mouth disease virus (FMDV)

Project description:The pathogen and host factors that contribute to the establishment of foot-and-mouth disease virus (FMDV) persistence are currently not understood. Using primary bovine soft palate multilayers in combination with RNA sequencing, we analyzed the transcriptional responses during acute and persistent FMDV infection.

2019-01-18 | E-MTAB-7605 | biostudies-arrayexpress

Foot and mouth disease virus (FMDV) infection in Indian cattle (Bos indicus): Profiling of serum microRNAs

Project description:Profiling of miRNA in serum of FMDV infected cattle, to understand disease pathogenesis and to identify FMD specific miRNA biomarkers to aid early pre-clinical diagnosis

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Development of gene expression for FMDV-infected RAW264.7 cell

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Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

Project description:Immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in micro-dissected compartments of the bovine nasopharynx were investigated using qRT-PCR and whole transcriptome microarray. Analysis of tissue samples obtained by laser capture microdissection (LCM) during transitional and persistent phases of infection demonstrated significant differences in transcriptome profiles of animals that cleared infection versus those that became persistently infected carriers. The combined output of the analyses suggested that clearance of FMDV from the nasopharyngeal mucosa is associated with an activated cellular immune response. This was supported by induction of Th1-associated mediators and upregulation of multiple targets associated with activation of T cell-mediated cytotoxicity in tissues from animals that cleared infection. Contrastingly, the pattern of gene regulation in FMDV carriers during transitional and persistent phases of infection suggested inhibition of T cell activation and promotion of Th2 polarization. Regulation of genes associated with apoptosis or cellular proliferation suggested inhibition of apoptotic pathways and promotion of cellular proliferation associated with FMDV persistence while the opposite patterns were found in animals that cleared infection. The findings presented herein emphasize the critical importance of Th1-mediated cellular immunity for clearance of persistent FMDV infection. Additionally, the strong antibody-mediated immune response that is induced during acute infection may impair efficient clearance of intra-cellular virus, thereby promoting FMDV persistence. Thus, a critical balance between Th1 and Th2 -mediated immunity is essential for successful clearance of FMDV infection and should be considered for development of next-generation vaccines and antiviral products.

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

Project description: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 type 2 immune polarization, as well as to the induction of regulatory T cells and T-cell exhaustion 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 that FMDV persistence in nasopharyngeal tissues of cattle is maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.

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Transcriptome analysis of total blood cells from sheep after vaccination with FMDV vaccines

Project description:Transcriptome analysis of total blood cells from sheep collected at 0, 4 and 24 hours after vaccination with inactivated FMDV vaccine, and adenovirus (human Ad5)-based vaccines encoding FMDV antigens, with and without Montanide ISA206 VG adjuvant.

2019-12-10 | GSE135609 | GEO

Cellular response to Foot-and-mouth disease virus (FMDV) infection in the BHK-21 transcriptome

Project description:We used RNA-sequencing on the Illumina platform to analyze transcriptome profiles of BHK-21 acutely infected with FMDV. In total, we obtained more than 342.8 million raw sequencing reads. And approximately 336.5 million clean reads (98.14%) were acquired by filtering out the adapters and trimming ambiguous reads. We found that cellular response of BHK-21 is related to certain types of alterations in the host cell transcriptome profiles at 24 h post infection.

2018-12-20 | GSE124122 | GEO

Raw microarray derived data for evaluation of a feature and template-assisted assembler for the analysis of foot-and-mouth disease virus by sequence assembly

Project description:Here we describe a custom FMDV microarray and a companion feature and template-assisted assembler software (FAT-assembler) capable of resolving virus genome sequence using a moderate number of conserved microarray features. The results demonstrate that this approach may be used to rapidly characterize naturally occurring FMDV as well as an engineered chimeric strain of FMDV. The FAT-assembler, while applied to resolving FMDV genomes, represents a new bioinformatics approach that should be broadly applicable to interpreting microarray genotyping data for other viruses or target organisms

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