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

ABSTRACT: 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

ORGANISM(S): Mesocricetus auratus

PROVIDER: GSE93045 | GEO | 2018/03/22

REPOSITORIES: GEO

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

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

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