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

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. Overall design: Epithelial tissue associated with lymphoid follicles in the dorsal nasopharynx or the dorsal soft palate of 15 Holstein cattle was obtained by laser-capture microdissection. RNA extracted from the tissues was amplified by REPLI-g whole-transcriptome amplification, heat-fragmented, labeled with Cy3 and Cy5 and hybridized to paired 4x45K arrays in a dye-swap arrangement. The numbers of FMDV carriers, non-carriers and controls were unbalanced, precluding a fully connected dye-swap design, and a separate-channel approach using a common correlation model (Smyth and Altman, 2013, BMC Bioinformatics 14:165, doi: 10.1186/1471-2105-14-165) was used instead.

Bibliographic Details

Main Author:	PIADC, Foreign Animal Disease Research Unit, USDA-ARS (18796294)
Format:	Dataset biblioteca
Published:	2017
Subjects:	Genetics, Bos taurus, eEukaryotes,
Online Access:	https://figshare.com/articles/dataset/Clearance_of_a_persistent_picornavirus_infection_is_associated_with_enhanced_pro-apoptotic_and_cellular_immune_responses/25082510
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