Investigating the Role of Cytokines in Immunity to Marek's Disease

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Investigating the Role of Cytokines in Immunity to Marek's Disease

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Title: Investigating the Role of Cytokines in Immunity to Marek's Disease
Author: Haq, Kamran
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Sharif, Shayan
Abstract: Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by an oncogenic herpesvirus, Marek’s disease virus (MDV). Despite the availability of MD vaccines, little is known about the underlying immunological mechanisms that mediate vaccine-induced immunity. The objective of this research was to elucidate these mechanisms. To characterize host responses in the lungs, chickens were vaccinated with herpesvirus of turkeys (HVT) and infected with MDV-RB1B. Vaccinated MDV-infected chickens had a higher accumulation of viral genome in the lungs, associated with T cell infiltration in lung tissue and an up-regulation of interferon (IFN) - and interleukin (IL) -10. This finding led us to conclude that IFN-γ has a role in immunity; hence, we further investigated the role of this cytokine. The hypothesis tested was that the protective efficacy of HVT against MDV-RB1B would be enhanced when combined with recombinant chicken IFN-γ (rChIFN-). Chicken IFN-γ coding sequence was cloned into an expression plasmid, and the bioactivity of rChIFN- was confirmed. Administration of this plasmid led to a significant reduction in tumour occurrence in HVT vaccinated MDV-infected chickens, suggesting enhanced vaccine-induced immunity. To shed more light on the relevance of IFN-γ to immunity against MD, studies were designed to down-regulate the expression of IFN-γ in chicken tissues. Three small interfering (si)RNAs specific for chicken IFN- were selected which significantly inhibited expression of IFN-γ by up to 80% in cultured cells. These three siRNAs and a non-target control were cloned and expressed as short hairpin RNA (shRNA) using an avian adeno-associated virus (rAAAV) vector system. An MDV challenge trial was conducted once shRNA expression by the rAAAV was confirmed in vitro. It was reasoned that down-regulation of IFN- would lead to abrogation of immunity conferred by HVT. There was an increase in the number of chickens with tumours that received HVT and rAAAV + IFN-γ shRNA compared to the control group, though not statistically significant. However, no difference in MDV genome load in feathers was detected between vaccinated MDV-infected birds with or without rAAAV. In summary, we have demonstrated here that cytokines are induced in the course of vaccination against Marek’s disease and that IFN-γ plays a role in vaccine-induced immunity against MD.
URI: http://hdl.handle.net/10214/3635
Date: 2012-05-14


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