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United States Department of Agriculture

Agricultural Research Service

Research Project: GENETIC AND BIOLOGICAL DETERMINANTS OF AVIAN TUMOR VIRUS PATHOGENICITY, TRANSMISSION, AND EVOLUTION

Location: Avian Disease and Oncology Laboratory

Title: Marek’s disease virus-induced transient cecal tonsil atrophy

Authors
item Heidari, Mohammad
item Fitzgerald, Scott -
item Zhang, Huanmin

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 24, 2014
Publication Date: N/A

Interpretive Summary: Marek’s disease (MD) causes enormous economical losses to the poultry industry. Marek’s disease virus (MDV), the etiological agent of MD, is a herpes virus that causes the suppression of immune system and evasion of immune responses in the infected chickens. MD is characterized by atrophy of bursa and thymus, anemia, weight loss, neurological disorders and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves. The cecal tonsils (CT) are considered the largest lymphoid aggregates of avian gut-associated lymphoid tissue (GALT). Along with Peyer’s patches, CT elicits protective immune responses against bacterial and viral pathogens in the intestinal tract of avian species. In this study, we investigated the effect of MDV infection on CT structural changes and host gene expression in two MD-susceptible and resistant chicken lines. The histopathological analysis revealed that MDV causes the loss of germinal follicular centers within the CT of the resistant line while inducing a severe near total lymphoid depletion in the susceptible line during early phase of infection. The lymphoid depletion, however, recovered approximately two weeks post infection but the loss of germinal centers persisted during the latent phase of infection in both lines. The atrophy of this important GALT was transient and there were no visible differences between the CT of the infected and control birds of either line by 21 days post infection. Gene expression analysis revealed a strong immune response within the CT of the susceptible line than the resistant line. Higher transcriptional activities of immune-related genes in the CT of the susceptible line is suggestive of a severe infection and consequently, stronger immune responses to viral antigen. This information should help us to better understand immunopathogeneis of this disease, and consequently, design better control methods.

Technical Abstract: Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. MD is characterized by bursal/thymic atrophy and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves with severe clinical symptoms that include transient paralysis, anemia, weight loss, and neurological disorders. The cecal tonsils (CT) are considered the largest lymphoid aggregates of avian gut-associated lymphoid tissue (GALT). Along with Peyer’s patches, CT elicits protective immune responses against bacterial and viral pathogens in the intestinal tract of avian species. In this study, we investigated the effect of MDV infection on CT structural changes and cytokine gene expression in two MD-susceptible and resistant chicken lines. The histopathological analysis revealed that MDV causes the loss of germinal follicular centers within the CT of the resistant line while inducing a severe near total lymphoid depletion in the susceptible line during cytolytic infection. The lymphoid depletion, however, recovered approximately two weeks post infection but the loss of germinal centers persisted during the latent phase of infection in both lines. The atrophy of this important GALT was transient and there were no visible differences between the CT of the infected and control birds of either line by 21 days post infection. Of the genes tested, IFN-' and IFN-' were up regulated in the CT of both infected lines during lytic infection. The expression levels of both genes were much higher in the susceptible line than the resistant line. Similar pattern of expression was observed for IL-6, IL-10, IL-13, and iNOS. IL-12 was up regulated in the CT of birds of the susceptible line during all three phases of infection. An over expression of IL-18 was also observed in CT of the susceptible line during lytic and latent phases of infection. IL-8 was the only cytokine expressed at higher levels in the CT of the resistant line during the lytic and reactivation phases of infection.

Last Modified: 10/23/2014
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