Th17 cell differentiation induced by cytopathogenic biotype BVDV-2 in bovine PBLCs

Abstract

Background Bovine viral diarrhea virus (BVDV) is a major pathogen that causes bovine viral diarrhea/mucosal disease (BVD-MD), which has become a global infectious disease due to its wide spread and the lack of effective treatment. The process of BVDV infection is complex. Once infected, host immune cells are activated and modulated. As a major immune cell, peripheral blood lymphocyte cells (PBLCs) are the primary target of BVDV. In order to further understand the mechanism of BVDV- host interaction, the expression profiles of host lymphocytes mRNAs associated with BVDV infection were investigated by transcriptomic sequencing analysis. Results The transcriptomic sequencing analysis was performed on bovine PBLCs infected with CP BVDV-2 GS2018 after 12 h of infection. Gene expression profiling demonstrated that 1052 genes were differentially expressed in GS2018 infected PBLCs compared with the control group. Of these genes, 485 genes were up-regulated and 567 were down-regulated. The 19 differential expressed genes (DEGs) were selected for validation using quantitative real-time PCR and the results were consistent with the results of RNA-Seq. Gene ontology enrichment and KEGG pathway analysis showed that 1052 DEGs were significantly enriched in 16 pathways, including cytokine-cytokine receptor interaction, IL17, PI3K-Akt, MAPK and TNF signaling pathway. PPI network analysis showed that IL17A, IFN-γ and TNF-α interacted with various proteins and may play crucial roles in BVDV-2 infection. Of note, we confirmed that GS2018 induced Th17 cell differentiation in PBLCs and persistently increased the expression levels of IL17A. In turn, the replication of GS2018 was inhibited by IL17A. Conclusion In this study, the transcription changes of DEGs related to host immune responses in bovine PBLCs were caused by CP BVDV-2 infection. In particular, the effector molecules IL17A of Th17 cells were significantly up-regulated, which inhibited viral replication. These results will contribute to exploration and further understanding of the host immune response mechanism and interaction between host and BVDV-2.

miR-216b-5p Inhibited the Progression of Experimental Optic Neuritis via Downregulating FAS

“…In addition, overexpression of FAS exacerbated experimental optic neuritis by promoting the inflammatory response and Th17 cell differentiation, and miR-216b-5p reversed this effect. Th17 cells are a subset of CD4 + T cells that mainly secrete IL-17 [ 20 ]. Numerous experiments showed that Th17 cells and their associated cytokines were closely related to the onset of ON and the activity of the disease [ 21 ].…”

Non-structural proteins of bovine viral diarrhea virus

“…The clinical features of cows with the mucosal disease are hemorrhagic, necrotic, and ulcerative lesions. In addition, it is often manifested as loss of intestinal gland crypts, erosions, ulcers, and large-scale mucosal necrosis in part or throughout the entire gastrointestinal system [ 16 ]. PI animals with BVDV-1 or BVDV-2 are immune-tolerant to BVDV, carry the virus for life, and excrete the virus to become a new source of infection in the animal population, making it difficult to eradicate the disease [ 17 – 19 ].…”