Marek's Disease Virus Induced Immunological Response Gene Expression Profile And MiRNA Regulation Roles In Tumor Developing

Marek's disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated immunosuppressive oncogenicα-herpes virus, MD virus (MDV). After a brief burst of productive/restrictive infection in B cells, a latent infection in CD4+ T lymphocytes occurs at about 7 days post infection (dpi) that lasts up to two weeks prior to virus reactivation and tumor development. The latently infected T lymphocytes are the means of virus dissemination to the skin and feather follicle epithelial cells, where fully infections enveloped cell-free virus particles are produced and released into the environment. The subsets of latently infected transformed CD4+ T cells that harbor MDV genome, migrate through the blood stream, and establish lymphomas in the skin, visceral organs, and peripheral nerves.In this study, the seletected immune- and nonimmune-related genes were tested in the spleen tissues of rMd5- and rMd5?meq-infected chickens at 5 dpi by the Real-Time RT-PCR methods. The results showed that both rMd5 and rMd5?meq can cause strong immune response in the infected chickens, and the meq gene had no significant impact on the gene expression profile. In addition, a reduction in the transcriptional activity of Bcl-2 in recombinant fowlpox virus (rFPV)+meq-infected chicken embryonic fibroblasts suggested that meq alone did not impede, but accelerated FPV-induced apoptosis.The microarray data also supported the profile analysis above, and showed the meq gene was important for the virus reactivation and replication at 21 dpi. While, Both rMd5- and rMd5?meq-infection involved in the host immune respose-IFNα/βsignaling pathway and antivirial action of interferons which were activated and suppressed, repectively at 5dpi and 21 dpi. Also, those interested genes, such as MMP-13, Mx, IFN-γ, VLIG-1, Bcl2l14 and Bu-1a, were tested by Real-Time RT-PCR to illuminate the roles in pro/anti– tumor or–apoptosis progress with the MDV infection. All the results indicated that the immune system of chicken possessed a strong antiviral, anti-tumor and pro-apoptosis effection at the initial MDV infection phase, but these kinds of host abilities were supressed immediately after the latence infection and reactivation of virus, which created a great condition for virus infection and tumor developing in the later period of MDV activity.In order to illuminate the miRNA roles in the MDV-induced tumor developing, gga-miR-181a, gga-miR-21, and also the related genes, such as Fas L, FIGN, HOXA11, and etc, were choosed to determine their relationship during the progress of MSB-1 cell induced to apoptosis or proliferation. The results indicated that both gga-miR-181a and -21 were involved in and correlated positively with the programmed cell death. In addition, FIGN and HOXA11 possessed great abilities of anti-apoptosis and promotion of tumor cell proliferation, which were regulated by gga-miR-21, at least, in the CD4+ T lymphoma.