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THE ROLE OF INTERFERON AND NON-CONVENTIONAL T-CELLS IN THE CLEARANCE OF PRIMARY BHV-1 RESPIRATORY INFECTION

dc.contributor.advisorGriebel, Philip J
dc.contributor.committeeMemberMutwiri, George
dc.contributor.committeeMemberTikoo, Suresh
dc.creatorOsman, Rahwa A 1982-
dc.creator.orcid0000-0001-5244-1623
dc.date.accessioned2018-03-23T20:52:48Z
dc.date.available2018-03-23T20:52:48Z
dc.date.created2018-02
dc.date.issued2018-03-23
dc.date.submittedFebruary 2018
dc.date.updated2018-03-23T20:52:49Z
dc.description.abstractBovine herpesvirus-1 (BHV-1) is prevalent globally and is an important cause of bovine disease. Humoral and cell-mediated immune responses contribute to viral clearance following a primary BHV-1 respiratory infection but innate immune mechanisms contributing to early control of BHV-1 infection are not known. Gene expression analyses and immunohistochemical (IHC) studies were used to investigate the role of interferons (IFNs) and innate immune cells during a primary BHV-1 infection. There was significant (P < 0.05) induction of type I IFN and IFN-stimulated genes (ISGs) in the URT within 3 days post-infection (pi) but virus shedding continued for another 4 to 7 days. In vitro studies demonstrated that both type I and II IFNs had limited capacity to inhibit BHV-1 replication and BHV-1 infection did not block ISG transcription. Consequently, immune cell recruitment to the URT was analyzed following BHV-1 infection to determine if alternative defence mechanisms were activated. Morphometric analyses of lymphocytes in URT tissues before and after BHV-1 infection revealed significant (P < 0.05) increases in cell populations expressing CD335+ (NKp46 natural cytotoxicity receptor), CD3+ (T-cell lineage marker) and CD8+ (cytotoxic T-cell marker) on day 5 pi. Confocal microscopy confirmed that approximately 90% of lymphocytes present on day 5 pi were T-cells co-expressing CD335 and CD8. This bovine T-cell subpopulation is known as non-conventional T cells, which may be innate lymphocytes. Specific recruitment of non-conventional T-cells to the site of BHV-1 infection in the URT raised questions regarding what chemokines may be involved in regulating this selective cell migration. Chemokine(s) involved in non-conventional T-cell recruitment in cattle are currently not known. qRT-PCR analysis of known bovine chemokine genes revealed that the expression of CCL4, CCL5 and CXCL9 genes were significantly (P < 0.05) up-regulated following BHV-1 infection in nasal turbinates. Thus, one or more of these chemokines may be involved in the selective recruitment of bovine non-conventional T-cells to the site of BHV-1 infection. The specific recruitment of non-conventional T cells to infected tissue suggests these cells may play an important role in either viral clearance or regulating host responses during BHV-1 infection.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10388/8485
dc.subjectInterferon
dc.subjectinterferon-induced antiviral effectors
dc.subjectNon-conventional T-cells
dc.subjectBovine herpesvirus -1
dc.subjectlymphocyte recruitment
dc.subjectchemokines
dc.titleTHE ROLE OF INTERFERON AND NON-CONVENTIONAL T-CELLS IN THE CLEARANCE OF PRIMARY BHV-1 RESPIRATORY INFECTION
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentSchool of Public Health
thesis.degree.disciplineVaccinology and Immunotherapeutics
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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