|DELEKTA, PHILLIP - Orise Fellow|
Submitted to: Viral Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2017
Publication Date: N/A
Interpretive Summary: Marek’s disease virus (MDV), the etiological agent of Marek’s disease (MD), is a herpes virus that causes the suppression of immune system and evasion of immune responses in the infected chickens. The feather follicle epithelial cells of the skin are the only anatomical sites where infectious enveloped cell-free virus particles are produced and disseminated into the environment. The mechanisms by which MDV infects skin and feather follicles are poorly understood. In this study we investigated the immunosuppressive effect of MDV infection on the host gene expression pattern in the skin of MDV-infected chickens. Our data revealed substantial changes in the gene expression profiling of the MDV-infected skin when compared to the uninfected control birds. Analysis of the differentially expressed genes resulted in the identification of several gene categories, with most being involved in host immune responses. Among the highly up-regulated genes, we identified 6 genes with known immunosuppressive properties. The significant up-regulation of these host immune-related genes is likely the result of MDV-induced immunosuppressive mechanism for viral immune evasion. Identification and characterization of these genes will provide tools for development of new and efficacious vaccines that would induce sterile immunity and prevent virus dissemination and evolution toward higher virulence.
Technical Abstract: Marek’s disease virus, a highly cell-associated oncogenic 'alpha-herpesvirus, is the causative agent of a T cell lymphoma and neuropathic disease called Marek’s disease. The skin is the only anatomical site where infectious enveloped cell-free virions are produced and shed into the environment. Studies have demonstrated that Marek’s disease virus infection induces immunological responses within the skin, including the release of cytokines and the recruitment of T lymphocytes. The host immune response, however, is not sufficient to block replication and shedding of the virus particles from the skin. In this study, we examined alterations to the host global gene expression pattern in the skin of Marek’s disease virus-infected chickens to identify candidate genes associated with Marek’s disease virus-induced immunosuppression. To identify these genes in an unbiased and comprehensive manner, we performed RNA-seq on skin samples of Marek’s disease virus-infected chickens at 10, 20 and 30 days post infection. In total, we identified 923 up and 409 down regulated genes in the skin of MDV-infected chickens when compared with uninfected controls. Analysis of the up-regulated genes resulted in the identification of multiple gene ontology categories, with most falling under the host immune response. Searching these immune related gene ontology categories, we identified six genes, gga-let-7d, IL22RA2, TNFRSF21, Pstpip2, SOCS1 and SOCS3, with known immunosuppressive properties that are up regulated in the skin of Marek’s disease virus-infected chickens.