Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The early pathogenesis of Marek's disease virus (MDV) infection is characterized by a lytic infection followed by the induction of latency. Genetically resistant N2a and susceptible P2a chickens were infected with the less virulent JM-16 or the very virulent plus (vv+) RK-1 MDV strains to examine the relationship between virulence and resistance on virus replication during 1-10 days postinfection (dpi) using real-time quantitative polymerase chain reaction (qPCR) and quantitative reverse transcriptase (qRT)-PCR assays. The numbers of copies of the viral DNA or transcripts amplified by these assays were normalized relative to cellular controls and subjected to three-way ANOVA. Viral DNA but not RNA was present in spleens at 1-3 dpi in decreasing quantities, and at 4 dpi, viral DNA started to increase concomitant with the initiation of viral transcription independently of virus strain and genetic resistance. At 6 dpi, JM-16 became latent in resistant N2a and susceptible P2a chickens with low levels of viral transcripts, but transcriptional activity increased in susceptible P2a chickens at 9 and 10 dpi. In contrast, infection with vv+ RK-1 never went into latency in both chicken lines. Viral transcripts were present from 4 to 10 dpi showing a higher and more persistent viral activity that may lead to severe damage to the lymphoid organs resulting in increased immunosuppression and increased incidence of MD. The use of qPCR and qRT-PCR to determine viral DNA load and transcriptional activity may offer an alternative to the current system of pathotyping to characterize new MDV isolates.
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PMID:Association between rate of viral genome replication and virulence of Marek's disease herpesvirus strains. 1538 Mar 65

Telomerase is a ribonucleoprotein complex consisting of two essential core components: a reverse transcriptase and an RNA subunit (telomerase RNA [TR]). Dysregulation of telomerase has been associated with cell immortalization and oncogenesis. Marek's disease herpesvirus (MDV) induces a malignant T cell lymphoma in chickens and harbors in its genome two identical copies of a viral TR (vTR) with 88% sequence identity to chicken TR. MDV mutants lacking both copies of vTR were significantly impaired in their ability to induce T cell lymphomas, although lytic replication in vivo was unaffected. Tumor incidences were reduced by >60% in chickens infected with vTR- viruses compared with animals inoculated with MDV harboring at least one intact copy of vTR. Lymphomas in animals infected with the vTR- viruses were also significantly smaller in size and less disseminated. Constitutive expression of vTR in the chicken fibroblast cell line DF-1 resulted in a phenotype consistent with transformation as indicated by morphological alteration, enhanced anchorage-independent cell growth, cell growth beyond saturation density, and increased expression levels of integrin alpha v. We concluded that vTR plays a critical role in MDV-induced T cell lymphomagenesis. Furthermore, our results provide the first description of tumor-promoting effects of TR in a natural virus-host infection model.
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PMID:A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis. 1668 1

Marek's disease virus (MDV) is an alphaherpesvirus that induces a highly malignant T-lymphoma in chickens. The viral genome encodes two identical copies of a viral telomerase RNA subunit (vTR) that exhibits 88% sequence identity to its chicken ortholog chTR. The minimal telomerase ribonucleoprotein complex consists of a protein subunit with reverse transcriptase activity (TERT) and an RNA subunit (TR). The active complex compensates for the progressive telomere shortening that occurs during mitosis and is involved in the cell immortalization process. We show here that the upregulation of telomerase activity is associated with an increase in vTR gene expression in chickens infected with the highly oncogenic MDV strain RB-1B. A comparative functional analysis of the viral and chicken TR promoters, based on luciferase reporter assays, revealed that the vTR promoter was up to threefold more efficient than the chTR promoter in avian cells. We demonstrated, by directed mutagenesis of the vTR promoter region, that the stronger transcriptional activity of the vTR promoter resulted largely from an E-box located two nucleotides downstream from the transcriptional start site of the vTR gene. Furthermore, transactivation assays and chromatin immunoprecipitation assays demonstrated the involvement of the c-Myc oncoprotein in the transcriptional regulation of vTR. Finally, an Ets binding site was specifically implicated in the transcriptional regulation of vTR in the MDV-transformed lymphoblastoid cell line MSB-1.
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PMID:Involvement of the oncoprotein c-Myc in viral telomerase RNA gene regulation during Marek's disease virus-induced lymphomagenesis. 1731 64

Polymerase chain reaction (PCR)-based approaches to the detection, differentiation and characterization of avian pathogens continue to be developed and refined. The PCRs, or reverse transcriptase-PCRs, may be general, designed to detect all or most variants of a pathogen, or to be serotype, genotype or pathotype specific. Progress is being made with respect to making nucleic acid approaches more suitable for use in diagnostic laboratories. Robotic workstations are now available for extraction of nucleic acid from many samples in a short time, for routine diagnosis. Following general PCR, the DNA products are commonly analyzed by restriction endonuclease mapping (restriction fragment length polymorphism), using a small number of restriction endonucleases, based on a large body of sequence data. Increasingly, however, nucleotide sequencing is being used to analyze the DNA product, in part due to the expanding use of non-radioactive sequencing methods that are safe and enable high throughout. In this review, I highlight some recent developments with many avian viruses: Newcastle disease virus; circoviruses in canary and pigeon; infectious bursal disease virus (Gumboro disease virus); avian adenoviruses, including Angara disease/infectious hydropericardium virus, haemorrhagic enteritis virus of turkeys, and egg drop syndrome virus; avian herpesviruses, including infectious laryngotracheitis virus, duck plague virus, psittacine herpesvirus (Pacheco's parrot disease virus), Marek's disease virus and herpesvirus of turkeys; avian leukosis virus (associated with lymphoid leukosis or myeloid leukosis, and egg transmission); avian pneumoviruses (turkey rhinotracheitis virus); avian coronaviruses, including infectious bronchitis virus, turkey coronavirus and pheasant coronavirus; astrovirus, in the context of poult enteritis and mortality syndrome, and avian nephritis virus; and avian encephalomyelitis virus, a picornavirus related to hepatitis A virus.
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PMID:Innovation and discovery: the application of nucleic acid-based technology to avian virus detection and characterization. 1918 52

Marek's disease virus (MDV) is an alphaherpesvirus that causes lethal T-cell lymphomas in chickens. MDV is unique in that it harbors two copies of a viral telomerase RNA subunit (vTR) in its genome exhibiting 88% sequence identity to the chicken orthologue, chTR. The minimal telomerase ribonucleoprotein complex consists of a protein subunit with reverse transcriptase activity (TERT) and TR. Physiologically, the complex compensates for the progressive telomere shortening that occurs during mitosis and is involved in the process of cellular immortalization. Previous studies showed that MDV vTR performes an auxiliary function during oncogenesis. Comparative in vitro analysis of the viral and chicken TR promoters revealed that the vTR promoter (PvTR) was up to 3-fold more efficient than the chTR promoter (PchTR) in avian cells and that the stronger transcriptional activity of PvTR resulted largely from an E-box located two nucleotides downstream of the transcriptional start site of the vTR gene. To test the hypothesis that PvTR is required for vTR expression and, hence, efficient tumor formation, we generated a recombinant virus, vPchTR+/+, in which the vTR promoter was replaced by that of chTR. In vivo, growth of vPchTR+/+ was indistinguishable from that of parental virus; however, tumor induction was reduced by >50% and lymphomas were smaller and less disseminated when compared to those induced by parental virus. We concluded that PvTR is not required for lytic replication in vivo but is essential for efficient transcription of vTR and thereby critical for efficient MDV lymphoma formation.
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PMID:Viral control of vTR expression is critical for efficient formation and dissemination of lymphoma induced by Marek's disease virus (MDV). 2042 96

The QT35 cell line, established from 20-methylcholanthrene (MCA)-induced tumours in Japanese quail, is positive for Marek's disease virus (MDV), and therefore we examined whether MDV is important for the development of MCA-induced tumours. Japanese quail were inoculated with the JM16 strain of MDV at 1 or 3 days of age or left uninoculated. At 3 weeks of age, quail were injected in the breast muscle with 4 mg MCA in corn oil or corn oil alone. Quail were observed for tumours three times/week and at post mortem at 11 to 12 weeks of age. MDV DNA was detected by polymerase chain reaction (PCR) in spleens of 14/20 birds inoculated with JM16+corn oil and of 53/71 birds inoculated with JM16+MCA. Interestingly, 1/74 quail was positive in the MCA group alone for MDV DNA. Tumours were collected for histopathology, cell line development, and PCR and reverse transcriptase-PCR for the presence of MDV. Tumours developed in 38/83 MCA-treated and 32/85 JM16+MCA-treated quail. Fibrosarcomas without metastasis were the only tumours observed in the MCA-treated quail, while quail treated with JM16 and MCA developed undifferentiated tumours, fibrosarcomas, lymphosarcomas or combinations with or without metastasis. One out of 20 quail receiving JM16 alone developed a lymphosarcoma. Cell line development was not influenced by JM16. Tumours from MCA-treated quail were negative for MDV, while 19/29 were positive in the JM16+MCA group. MDV transcripts were present in 13/18 tumours examined in the JM16+MCA group. In conclusion, MDV did not affect tumour development but did influence tumour aggression and histological type.
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PMID:Role of Marek's disease herpesvirus in the induction of tumours in Japanese quail (Coturnix coturnix japonica) by methylcholanthrene. 2054 24

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.
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PMID:Gene expression profiling in rMd5- and rMd5deltameq-infected chickens. 2201 31

The epidermal growth factor receptor (EGFR), a growth-factor-receptor tyrosine kinase, is up-regulated in numerous tumors, which provides a good target for cancer therapy. Although it has been documented that oncoviruses are responsible for the activation of EGFR in tumors, the impact of Marek's disease virus (MDV) infection on EGFR has not yet been studied. We performed quantitative reverse transcriptase (RT)-PCR to check EGFR expression and found that it was significantly down-regulated after MDV infection. To explore the mechanism of EGFR repression, we examined the level of methylation of the EGFR promoter. The methylation level was significantly increased at 21 days postinfection, indicating a potential role of promoter methylation in EGFR repression.
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PMID:DNA methylation down-regulates EGFR expression in chickens. 2390 48

The Toll-like receptor (TLR) signaling pathway is one of the innate immune defense mechanisms against pathogens in vertebrates and invertebrates. However, the role of TLR in non-MHC genetic resistance or susceptibility to Marek's disease (MD) in the chicken is yet to be elucidated. Chicken embryo fibroblast (CEF) cells from MD susceptible and resistant lines were infected either with Marek's disease virus (MDV) or treated with polyionosinic-polycytidylic acid, a synthetic analog of dsRNA, and the expression of TLR and pro-inflammatory cytokines was studied at 8 and 36 h posttreatment by quantitative reverse transcriptase PCR. Findings of the present study reveal that MDV infection and polyionosinic-polycytidylic acid treatment significantly elevated the mRNA expression of TLR3, IL6, and IL8 in both susceptible and resistant lines. Furthermore, basal expression levels in uninfected CEF for TLR3, TLR7, and IL8 genes were significantly higher in resistant chickens compared with those of susceptible chickens. Our results suggest that TLR3 together with pro-inflammatory cytokines may play a significant role in genetic resistance to MD.
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PMID:Differential expression of Toll-like receptor pathway genes in chicken embryo fibroblasts from chickens resistant and susceptible to Marek's disease. 2460 47

Marek's disease virus (MDV; also known as Gallid herpesvirus 2, MDV-1) causes oncogenic disease in chickens producing clinical signs that include lymphomas, visceral tumours, nerve lesions, and immunosuppression. MDV vaccines are widely used and mostly produced using primary cells: chicken embryo fibroblast cells, duck embryo fibroblast cells, chicken embryo kidney cells or chicken kidney cells. An immortalized cell line that can be used to manufacture the virus has long been desired. In this report, we demonstrate that QM7 cells were susceptible to infection with either MDV or herpesvirus of turkey (HVT; also known as Meleagrid herpesvirus 1, MDV-3). Polymerase chain reaction analysis with primers amplifying selected MDV genes revealed that QM7 cells did not contain these sequences. However, MDV genes were detected in QT35 cells, which have been reported to harbour latent MDV virus. Transfection of naked MDV DNA initiated efficient infection of QM7 cells. In addition, QM7 cell lysate, clarified supernatant, and QM7 cell pellet infected with MDV were negative for reverse transcriptase activity, indicating absence of endogenous retrovirus. QM7 cells were also found to be free of other avian pathogens in a chick embryo inoculation test. In vivo studies of MDV growing in QM7 cells showed the virus retained its pathogenicity and virulence. In ovo experiments demonstrated that both HVT and MDV propagated in QM7 cells did not interfere with hatchability of injected eggs, and viruses could be re-isolated from hatched chicks. The results suggest that QM7 could be a good host cell line for growing both MDV and HVT.
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PMID:Efficient Marek's disease virus (MDV) and herpesvirus of turkey infection of the QM7 cell line that does not contain latent MDV genome. 2520 14


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