Abstract
Bovine viral diarrhea virus (BVDV) is a pathogen associated with substantial economic losses in the dairy cattle industry. Currently, there are no effective vaccines against BVDV. Melatonin (MT) has been shown to have anti-inflammatory and anti-viral properties, and the use of MF59 in vaccines significantly enhances vaccine efficiency. Here, MT and MF59 were added into the Erns-LTB vaccine. Subsequently, their inhibitory activity on the NF-κB signaling pathway in Mardin-Darby Bovine Kidney cells and the hippocampus was assessed using western blot and quantitative reverse transcription PCR. The findings revealed that MT in the Erns-LTB vaccine decreases the phosphorylation of p65 proteins caused by BVDV infection. In addition, MT decreased the mRNA levels of IL-1β and IL-6 in vitro, but increased the production of IFN-α, IFN-β, Mx1 in vitro, brain-derived neurotrophic factor, cyclic amp response element-binding protein, and the stem cell factor in vivo. Furthermore, treatment with Erns-LTB + MF59 + MT stimulated the production of T lymphocytes, alleviated pathological damage, decreased expressions of BVDV antigen, and tight junction proteins in mice. These findings imply that MT has potential for use in the Erns-LTB vaccine to inhibit BVDV infection and regulate the immune responses of T-cells by inhibiting the NF-κB signaling pathway.
Highlights
Bovine viral diarrhea virus (BVDV) is a Pestivirus of the family Flaviviridae [1,2,3]endemic in wild and domestic animals worldwide [4,5]
There were no significant differences in proliferation among Mardin-Darby Bovine Kidney (MDBK) Cells treated with 0.1, 0.3, and 0.5 mM MT concentrations for 36 h and 48 h compared to the control
There were no significant differences in proliferation among MDBK Cells treated group (Figure S2)
Summary
Bovine viral diarrhea virus (BVDV) is a Pestivirus of the family Flaviviridae [1,2,3]endemic in wild and domestic animals worldwide [4,5]. Upon infection on a host, BVDV invades and damages multiple organs and tissues including the brain, kidney, lung, liver, intestine, and spleen by altering the major component of the cells such as the tight junction proteins (TJs) [6,7,8]. Tight junction proteins such as occludin and claudin-1 maintain epithelial barrier functions, their alterations increase the paracellular permeability [9] where BVDV uses them as co-receptors for cell entry [8]. This results in a decline in fecundity and milk production in dairy cows, leading to incalculable losses in the dairy industry [12,13]
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