Abstract
BackgroundBovine 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.ResultsThe 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.ConclusionIn 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.
Highlights
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
We focus on the expression levels of immune-related cytokines, especially IL17A, in bovine peripheral blood lymphocyte cells (PBLCs) infected with GS2018, which provides theoretical support for further research on the mechanism of host immune response and pathogenesis induced by BVDV infection
Differential expressed genes analysis To investigate the mRNA expression profile of PBLCs after GS2018 infection, the DEseq2 method was used to detect the differential expressed genes (DEGs) between the control (NC) and infection group (CP)
Summary
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. Bovine viral diarrhea virus (BVDV) is important pathogen related to bovine gastrointestinal, respiratory and reproductive diseases and causes serious bovine viral diarrhea/mucosal disease (BVD-MD), which has spread worldwide [1,2,3]. Except for the difference in pathogenicity (CP BVDV causes cell vacuolation, shedding and necrosis, but NCP BVDV does not), the genomes of CP and NCP BVDV-2 show obvious differences in the NS2/3 coding area. The novel CP BVDV-2 GS2018 strain isolated by our research group, is without inserted sequence in NS2/3 coding region, but showed significant cytopathic effect in MDBK cells, compared with other common CP BVDV
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