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The Indirect Effect of BVDV on Immune Suppression: The Role of Infected Macrophages in Lymphocyte Apoptosis

by Karim Abdelsalam

Institution:	South Dakota State University
Year:	2017
Keywords:	BVDV; immune dysfunction; immune suppression; indirect effect; lymphocyte apoptosis; macrophages; Veterinary Medicine; Veterinary Microbiology and Immunobiology; Veterinary Pathology and Pathobiology
Posted:	02/01/2018
Record ID:	2165532
Full text PDF:	http://openprairie.sdstate.edu/etd/1129

Abstract

BVDV is an important pathogen of cattle that affects both the dairy and beef industry causing severe economic losses. The main problem of BVDV is the immune suppression that is associated with lymphoid depletion shortly post infection. The mechanism of this immune suppression is not well understood. In this in vitro study, we sought to determine the indirect effect of BVDV infection in macrophages as a key player in the pathogenesis of BVD especially, the apoptotic effect induced on lymphocytes. We infected bovine monocyte-derived macrophages (MDM) with either high or low virulent strains of cytopathogenic or non-cytopathogenic strains of BVDV and collected supernatants that were used for treatment of the fresh peripheral blood lymphocytes or BL-3 B-cell line. We found that only supernatant from the high virulent BVDV strain induced lymphocyte apoptosis. Furthermore, direct infection of lymphocytes with the same virulent strain did not induce significant apoptosis. We investigated the apoptosis-related cytokine profile of the infected macrophages by qRT-PCP with different BVDV strains. There was no significant difference in the transcriptional profiles between strains so cytokine induction does not seem to be a mechanism of induced apoptosis. We then investigated the role of possible secreted viral proteins as the mechanism of indirect apoptosis of lymphocytes by treating the supernatants with specific antibodies against BVDV and its proteins. These treated supernatants still had lymphocyte apoptosis activity, ruling out their responsibility as well. Our data suggest an important role of macrophages in the mechanism of lymphocyte depletion by high virulent strains of BVDV, however further studies are required to determine the identity and mechanism of these apoptotic factors present in the supernatant of infected macrophages. Advisors/Committee Members: Christopher C.L. Chase.