Turkey B Cell Transcriptome Profile During Turkey Hemorrhagic Enteritis Virus (THEV) Infection Highlights Upregulated Apoptosis and Breakdown Pathways That May Mediate Immunosuppression.

Infection with the turkey hemorrhagic enteritis virus (THEV) can cause hemorrhagic enteritis, which affects young turkeys. This disease is characterized by bloody diarrhea and immunosuppression (IMS), which is attributed to apoptosis of infected B cells. Secondary infections due to IMS exacerbate economic losses. We performed the first transcriptomic analysis of a THEV infection to elucidate the mechanisms mediating THEV-induced IMS. After infecting and sequencing mRNAs of a turkey B-cell line, trimmed reads were mapped to the host turkey genome, and gene expression was quantified with StringTie. Differential gene expression analysis was followed by functional enrichment analyses using gprofiler2 and DAVID from NCBI. RT-qPCR of select genes was performed to validate the RNA-seq data. A total of 2343 and 3295 differentially expressed genes (DEGs) were identified at 12 hpi and 24 hpi, respectively. The DEGs correlated with multiple biological processes including apoptosis, ER unfolded protein response, and cell maintenance. Multiple pro-apoptotic genes, including APAF1, BMF, BAK1, and FAS were upregulated. Genes that play a role in ER stress-induced unfolded protein response including VCP, UFD1, EDEM1, and ATF4 were also upregulated and may contribute to apoptosis. Our data suggest that several biological processes and pathways including apoptosis and ER response to stress are important aspects of the host cell response to THEV infection. It is possible that interplay between multiple processes may mediate apoptosis of infected B-cells, leading to IMS.