Gene expression profiling in rMd5- and rMd5deltameq-infected chickens.
Marek's disease (MD) is a lymphoproliferative disorder of domestic chickens caused by a highly contagious and oncogenic alpha-herpesvirus, Marek's disease virus (MDV). 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 signs that include transient paralysis, anemia, weight loss, and neurologic disorders. Using overlapping cosmids- and BAC-cloned MDV, it has been shown that MDV-encoded vIL-8, pp38, vTR, vLIP, RLORF4, and meq are among the many essential genes that play critical roles in viral pathogenesis. Of all the genes investigated so far, only meq has been shown to be consistently expressed in all MDV-derived tumors and lymphoblastoid cell lines. Meq is a basic leucine-zipper protein that shares homology with the jun/fos family of transcriptional factors. There are two copies of meq gene within the MDV genome that are only present in the serotype-1 strains. It has been shown conclusively that deletion of meq results in loss of transformation of T cells in chickens, with no effect on the early cytolytic phase of infection in lymphoid organs, which is essential for induction of innate and adaptive immunity. The goal of this study was to investigate 1) the effect of the meq oncogene on the expression pattern of select chicken immune and nonimmune-related genes, and 2) its potential role in MDV-induced apoptosis. We used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profiling of a panel of chicken genes in rMd5- and rMd5deltameq-infected chickens at 5, 14, 21, and 35 days postinfection (dpi). Although the transcriptional activities of several immune-related genes, including IL-6, IL-10, cMGF, GM-CSF, iNOS, IFNbeta, and INFgamma, were higher in rMd5deltameq-infected chickens at 5 dpi when compared to the rMd5-infected birds, the differences in expression levels of the tested genes between the two viral constructs were not significant. In addition, a reduction in the transcriptional activity of Bdcl2 in recombinant fowlpox virus (rFPV)+meq-infected chicken embryonic fibroblasts suggested that meq alone did not impede FPV-induced apoptosis. The likely suppressive nature and anti-inflammatory function of the meq oncogene and its possible role in virus-induced cell death is discussed.
United States Department of Agriculture, Agriculture Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI 48823, USA.
Ming
M
Xu
Huanmin
H
Zhang
Lucy
L
Lee
Hongwei
H
Gao
Shayan
S
Sharif
Robert F
RF
Silva
Mohammad
M
Heidari
D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins / Q000235:genetics / Q000276:immunology; D002645:Chickens; D016207:Cytokines; D005587:Fowlpox virus / Q000502:physiology; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D025922:Mardivirus / Q000235:genetics*; D008380:Marek Disease / Q000235:genetics / Q000276:immunology* / Q000821:virology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D030161:Avian Proteins; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C059626:MGF protein, chicken; D009856:Oncogene Proteins, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II