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Title: Marek's disease virus induces Th-2 activity during cytolytic infection

Author
item Heidari, Mohammad
item Zhang, Huanmin
item SHARIF, SHAYAN - UNIV OF GUELPH, CANADA

Submitted to: Viral Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2008
Publication Date: 6/30/2008
Citation: Heidari, M., Zhang, H.M., Sharif, S. 2008. Marek's disease virus induces Th-2 activity during cytolytic infection. Viral Immunology. 21(2):203-213.

Interpretive Summary: Marek's disease (MD), a herpesvirus induced cancer like disease of chickens, is considered as a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but very little is known about the involvement of important mediators and regulators of host immune responses named cytokines. Functionally distinct host immune cells named T helper cells can be characterized according to the pattern of their cytokines production. T helper-1 type cells provide protection against intracellular pathogens including viruses. T helper-2 type cells, on the other hand, are involved in protection against extra-cellular organisms. In order to determine the involvement of T helper cells in pathogenesis of MD virus (MDV), we conducted a comprehensive cytokine gene expression analysis in tissues of MDV- infected chickens. Our results revealed that indeed a T helper-1 type of immune activity, that is so critical for the induction of a successful host antiviral immune response, is not predominant in chickens infected with extremely virulent strains of MDV known as vv+MDV. The data provided insights into the molecular mechanism of MDV virulence and essential role of cytokines in host antiviral immune responses. The information should be useful for future investigations aimed at developing new vaccines using cytokines as genetic adjuvant to amplify immune responses against MDV infection.

Technical Abstract: Marek’s disease (MD) is a lymphoproliferative disease of chickens that is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). The role of cytokines and other related proteins in MD pathogenesis and immunity is poorly understood. The aim of this study was to examine the transcriptional profiling of a panel of cytokines and other immune-related genes in the spleen tissues of chickens infected with a highly oncogenic strain of MDV during the cytolytic and latency infection. Real-Time PCR analysis revealed significant up-regulation in the expression levels of interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-13, interferon (IFN)-alpha, IFN-beta, IFN-gamma, chicken myelomonocytic growth factor (cMGF), granulocyte macrophage-colony stimulating factor (GM-CSF), and inducible nitric oxide synthase (iNOS) in the infected chickens at 5 days post inoculation (lytic infection). The changes in the mRNA levels of IL-18 and MHC I was minimal in comparison to the control birds. There was no significant difference in the expression levels of IL-2, IL-8, IL-12p40, Bcl-2, Bcl-x, Nr-13, and MHC II between the two groups. With the exception of IL-10 that showed persistent high transcriptional activities beyond the lytic phase, the expression pattern of all the tested genes were similar between the infected and age-matched control birds at 15 days post inoculation (latency infection). Of the genes examined, in addition to high transcriptional activities of IL-1beta, IL-6, iNOS, and type 1 and 2 IFNs, the relative expression levels of IL-4, IL-10, and IL-13 were among the highest in the infected chickens during the lytic phase of infection in comparison to the un-infected controls (9-50 fold difference). This observation suggests that (1) a Th2 type of immune response is induced by a very virulent plus MDV strain during the lytic phase of infection; and (2) there is no significant MDV-specific immune response in the latent phase of infection.