Transcriptome Analysis Reveals Inhibitory Effects of Lentogenic Newcastle Disease Virus on Cell Survival and Immune Function in Spleen of Commercial Layer Chicks

Abstract

As a major infectious disease in chickens, Newcastle disease virus (NDV) causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 days post inoculation (dpi) at day 21 with a lentogenic NDV in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV-challenged and non-challenged groups, 526 differentially expressed genes (DEGs) (false discovery rate (FDR) < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, Ingenuity Pathway Analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis, and angiogenesis. Up-regulation of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK signaling antagonist 1 (SPRY1), a DEG in the current study, is in a significant quantitative trait locus associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

Indicators of the molecular pathogenesis of virulent Newcastle Disease Virus in chickens revealed by transcriptomic profiling of spleen

“…Our IPA analysis also indicated the downregulation of some shared immune pathways with other in vivo NDV infections 20 . IL-8 signalling has a vital role during infectious disease by regulation of chemotaxis and activation of neutrophils 53 .…”

“…Zhang et al (2020) study has recently reported 31 pathways with consistent expression response to nonvirulent strains of NDV 20 . Comparison of predicted pathways in our study with impacted pathways by lentogenic NDVs, revealed 16 shared pathways (Table 4).…”

“…Further investigation into the functions of these uncharacterised proteins and genes would be useful to provide more insight into their contribution to infection. A list of DEGs with consistent responses in expression to NDV infection was released by Zhang et al (2020) 20 . Comparison of DEGs in our study with Zhang et al revealed 23 shared genes (Table 3).…”

“…Gene expression pattern analysis helps to understand the virus and host interactions. Several in vivo and in vitro studies investigated gene expression in different tissues from experimentally infected chickens with different genotypes of NDV [15][16][17][19][20][21] . However, the molecular pathogenesis of genotype VII of NDVs has not been well described especially in in vivo studies.…”

“…The spleen is the primary immune organ in birds and the place of maturation of B cells, antibody synthesises, screening of pathogens in peripheral blood and replication of leukocytes 18 . Recent in vivo studies revealed differential regulation of immune response to the lentogenic strain of NDV (LaSota) by transcriptome analysis in the spleen 19,20 . Another in vitro study compared transcript pro le of highly virulent Herts/33 strain and nonvirulent LaSota strain in spleen cells 21 .…”