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Genomics of host responses to Marek's disease virus

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Title: Genomics of host responses to Marek's disease virus
Author: Sarson, Aimie Jey
Department: Department of Pathobiology
Advisor: Sharif, Shayan
Abstract: To investigate genomics of the host response to Marek's disease virus (MDV), a 136 element, low-density chicken immune system-specific microarray was constructed, utilizing a bioinfomatic approach to identify known chicken immune system genes and to annotate chicken expressed sequence tags (ESTs). Microarray functionality was tested by gene expression profiling of lipopolysaccharide-stimulated chicken B cells. Differential gene expression was observed at 6, 12, and 24 hours post-stimulation. Intra- and interassay correlation coefficients were above 95 percent. The microarray was employed to investigate genes involved in host responses to MDV at 4, 7, 14, and 21 days post-infection. In vivo infection with very virulent MDV (RB1B) resulted in significant temporal changes in expression of immune-specfic genes in the spleen tissue. Specifically, Granzyme A, invariant chain, IgM, and CD3 genes were differentially expressed at more than one time point. To investigate gene expression profiles associated with resistance and susceptibility to Marek's disease, genetically-resistant ('B21') and--susceptible ('B19') birds were infected with a virulent strain of MDV (JM16). MDV infection resulted in significant differences in expression for genes in the spleen tissue, including chemokines (AH221 and lymphotactin), cell surface markers (CD107 and Bu-1), immunoglobulins (IgG and IgM), granzyme A and STAT-2 molecules. The up-regulation of granzyme A despite virus strain and chicken genotype led to the hypothesis that the sources of granzyme A (cytotoxic T lymphocytes (CTL) and natural killer (NK cells)), are integral to immunity to MDV. Therefore, to further dissect the mechanism of cytolysis within the spleen of MDV infected birds, real-time PCR was employed to determine expression patterns for genes within the granzyme A pathway. Genes encoding NK lysin and granzyme A were up-regulated at early time points following infection, coinciding with previous observations of NK cell and CTL cytotoxic activity following MDV infection. Overall, data obtained from both 'in vivo' experiments suggests, among other mechanisms, that antibodies and cytotoxic effector cells are potentially key mediators of the host response to MDV infection. These data illustrate that the host response to MDV within the spleen is dependent on the host genetic background, virulence strain of the infecting virus and the time point following infection.
Date: 2007
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