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

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 splenic tissues of chickens infected with a highly oncogenic strain of MDV during cytolytic infection and latency. Real-time polymerase chain reaction analysis revealed significant upregulation in the expression levels of interleukins (IL)-1 beta, IL-4, IL-6, IL-10, IL-12p35, and IL-13, interferons (IFN)-alpha, IFN-beta, and 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 d post-inoculation (lytic infection). The changes in the mRNA levels of IL-18 and MHC I were minimal in comparison to those of the control birds. There was no significant difference in the expression levels of IL-2, IL-8, MHC II, Bcl-2, Bcl-x, and Nr-13 between the two groups. With the exception of IL-10, which showed high transcriptional activity beyond the lytic phase, the expression patterns of all the tested genes were similar between the infected and age-matched control birds at 15 d post-inoculation (latency infection). Of the genes examined, in addition to the high transcriptional activities of IL-1 beta, IL-6, IL-12, iNOS, and type 1 and 2 IFNs, the relative expression levels of IL-4, IL-10, and IL-13 were significantly upregulated in the infected chickens during the lytic phase of infection compared to uninfected controls (a 9- to 50-fold difference). This observation suggests that (1) an immune response with a Th-2 characteristic 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.