Integrated Transcriptome and Histone Modification Analysis Reveals NDV Infection Under Heat Stress Affects Bursa Development and Proliferation in Susceptible Chicken Line

Two environmental factors, Newcastle disease and heat stress, are concurrently negatively impacting poultry worldwide and warrant greater attention into developing genetic resistance within chickens. Using two genetically distinct and highly inbred layer lines, Fayoumi and Leghorn, we explored how different genetic backgrounds affect the bursal response to a treatment of simultaneous Newcastle disease virus (NDV) infection at 6 days postinfection (dpi) while under chronic heat stress. The bursa is a primary lymphoid organ within birds and is crucial for the development of B cells. We performed RNA-seq and ChIP-seq targeting histone modifications on bursa tissue. Differential gene expression revealed that Leghorn, compared to Fayoumi, had significant down-regulation in genes involved in cell proliferation, cell cycle, and cell division. Interestingly, we also found greater differences in histone modification levels in response to treatment in Leghorns than Fayoumis, and biological processes enriched in associated target genes of H3K27ac and H3K4me1 were similarly associated with cell cycle and receptor signaling of lymphocytes. Lastly, we found candidate variants between the two genetic lines within exons of differentially expressed genes and regulatory elements with differential histone modification enrichment between the lines, which provides a strong foundation for understanding the effects of genetic variation on NDV resistance under heat stress. This study provides further understanding of the cellular mechanisms affected by NDV infection under heat stress in chicken bursa and identified potential genes and regulatory regions that may be targets for developing genetic resistance within chickens.