Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus

Abstract

Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection. The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-κB signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells. Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well. The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis. This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.

Novel Combined Tissue Transcriptome Analysis After Lentogenic Newcastle Disease Virus Challenge in Inbred Chicken Lines of Differential Resistance

“…Two inbred chicken lines have been shown to differ in their susceptibility to lentogenic La Sota NDV (Deist et al, 2017b). The Leghorn line (GHs 6) originated from a cross of two commercial lines in the 1950s and the Fayoumi line (M 15.2) originated from the Fayoum region of Egypt (Lamont and Chen, 1992).…”

“…Because the transcriptome is not stagnant, a more comprehensive physiological picture can be obtained by an integrative analysis of the transcriptomes of multiple tissues at multiple time points after a treatment. Previously, the trachea epithelial cells, lung, and Harderian gland of Fayoumis and Leghorns at 2, 6, and 10 days post-infection (dpi) with lentogenic NDV have been individually analyzed with RNA-seq (Deist et al, 2017a;Deist et al, 2017b;Deist et al, 2018). The three tissues had very distinct responses to NDV (Deist et al, 2017a;Deist et al, 2017b;Deist et al, 2018).…”

Genetic responses of inbred chicken lines illustrate importance of eIF2 family and immune-related genes in resistance to Newcastle disease virus

“…In the current study, the observed time effect on the expression of IFNB may help to explain the different rates of viral clearance between lines, as the Fayoumi had lower viral load than the Leghorn at 6 dpi 19,20 . Recognition of viral RNA by TLR7 triggers signaling for cytokines with antiviral activity to be upregulated 29 .…”

“…At 21 days of age, half of the chickens were inoculated with 200 µl of 10 7 EID 50 of La Sota NDV (NDV challenged group, n = 49) through nasal and ocular inoculation routes. The other chickens received 200 µl of phosphate-buffered saline (PBS) (nonchallenged group, n = 40) through same conditions, as described in [19][20][21] . The chickens from both lines and challenge statuses (NDV challenged or nonchallenged) were euthanized with sodium pentobarbital solution at 2 or 6 dpi.…”

“…Because Fayoumis had faster NDV clearance than the Leghorns as previously reported 20 , we also evaluated the differences between lines in the expression of eIF2 family-related genes to better understand how NDV replication may be delayed by host protein synthesis shut-off (Table 1; Fig. 3).…”