scholarly journals Telomerase flies the coop: the telomerase RNA component as a viral-encoded oncogene

2006 ◽  
Vol 203 (5) ◽  
pp. 1143-1145 ◽  
Author(s):  
Steven E. Artandi
Keyword(s):  
Disease Virus ◽  
Mouse Models ◽  
Marek's Disease Virus ◽  
Tumor Formation ◽  
Human Cells ◽  
Marek's Disease ◽  
Cancer Development ◽  
Telomerase Rna ◽  
Marek’S Disease Virus ◽  
Human Cancers

Telomerase, the enzyme that elongates our telomeres, is crucial for cancer development based on extensive analyses of human cells, human cancers, and mouse models. New data now suggest that a viral telomerase RNA gene encoded by Marek's disease virus (MDV), an oncogenic herpesvirus of chickens, promotes tumor formation. These findings highlight the importance of telomerase in cancer and raise new questions regarding the mechanisms by which the telomerase RNA component supports tumorigenesis.

scholarly journals Comparison of the Transcriptomes and Proteomes of Serum Exosomes from Marek’s Disease Virus-Vaccinated and Protected and Lymphoma-Bearing Chickens

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 116 ◽  
Author(s):  
Sabari Nath Neerukonda ◽  
Phaedra Tavlarides-Hontz ◽  
Fiona McCarthy ◽  
Kenneth Pendarvis ◽  
Mark S. Parcells
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Tumor Formation ◽  
Marek's Disease ◽  
Poultry Production ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Viral Mrnas ◽  
Serum Exosomes

Marek’s disease virus (MDV) is the causative agent of Marek’s disease (MD), a complex pathology of chickens characterized by paralysis, immunosuppression, and T-cell lymphomagenesis. MD is controlled in poultry production via vaccines administered in ovo or at hatch, and these confer protection against lymphoma formation, but not superinfection by MDV field strains. Despite vaccine-induced humoral and cell-mediated immune responses, mechanisms eliciting systemic protection remain unclear. Here we report the contents of serum exosomes to assess their possible roles as indicators of systemic immunity, and alternatively, tumor formation. We examined the RNA and protein content of serum exosomes from CVI988 (Rispens)-vaccinated and protected chickens (VEX), and unvaccinated tumor-bearing chickens (TEX), via deep-sequencing and mass spectrometry, respectively. Bioinformatic analyses of microRNAs (miRNAs) and predicted miRNA targets indicated a greater abundance of tumor suppressor miRNAs in VEX compared to TEX. Conversely, oncomiRs originating from cellular (miRs 106a-363) and MDV miRNA clusters were more abundant in TEX compared to VEX. Most notably, mRNAs mapping to the entire MDV genome were identified in VEX, while mRNAs mapping to the repeats flanking the unique long (IRL/TRL) were identified in TEX. These data suggest that long-term systemic vaccine-induced immune responses may be mediated at the level of VEX which transfer viral mRNAs to antigen presenting cells systemically. Proteomic analyses of these exosomes suggested potential biomarkers for VEX and TEX. These data provide important putative insight into MDV-mediated immune suppression and vaccine responses, as well as potential serum biomarkers for MD protection and susceptibility.

scholarly journals A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Andelé M. Conradie ◽  
Luca D. Bertzbach ◽  
Nirajan Bhandari ◽  
Mark Parcells ◽  
Benedikt B. Kaufer
Keyword(s):  
Disease Virus ◽  
Marek's Disease Virus ◽  
Tumor Formation ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Transactivation Domain ◽  
Marek’S Disease ◽  
Recombinant Viruses ◽  
Neurological Signs ◽  
Important Evidence

ABSTRACT Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek’s disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neurological signs, and fatal lymphomas, a process that requires the viral oncogene, meq. The most frequently used Marek’s disease vaccine is the live-attenuated CVI988/Rispens (CVI) strain, which efficiently protects chickens and prevents tumorigenesis. Intriguingly, CVI expresses at least two isoforms of meq; however, it remains unknown to what extent these isoforms contribute to virus attenuation. In this study, we individually examined the contribution of the two CVI-meq isoforms to the attenuation of the vaccine. We inserted the respective isoforms into a very virulent MDV (strain RB-1B), thereby replacing its original meq gene. Surprisingly, we could demonstrate that the longer isoform of meq strongly enhanced virus-induced pathogenesis and tumorigenesis, indicating that other mutations in the CVI genome contribute to virus attenuation. On the contrary, the shorter isoform completely abrogated pathogenesis, demonstrating that changes in the meq gene can indeed play a key role in virus attenuation. Taken together, our study provides important evidence on attenuation of one of the most frequently used veterinary vaccines worldwide. IMPORTANCE Marek’s disease virus (MDV) is one of several oncogenic herpesviruses and causes fatal lymphomas in chickens. The current “gold standard” vaccine is the live-attenuated MDV strain CVI988/Rispens (CVI), which is widely used and efficiently prevents tumor formation. Intriguingly, CVI expresses two predominant isoforms of the major MDV oncogene meq: one variant with a regular size of meq (Smeq) and one long isoform (Lmeq) harboring an insertion of 180 bp in the transactivation domain. In our study, we could break the long-standing assumption that the Lmeq isoform is an indicator for virus attenuation. Using recombinant viruses that express the different CVI-meq isoforms, we could demonstrate that both isoforms drastically differ in their abilities to promote pathogenesis and tumor formation in infected chickens.

scholarly journals The Marek’s disease virus unique gene MDV082 is dispensable for virus replication but contributes to a rapid disease onset

2021 ◽  
Author(s):  
Yu You ◽  
Andelé M. Conradie ◽  
Ahmed Kheimar ◽  
Luca D. Bertzbach ◽  
Benedikt B. Kaufer
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Rapid Onset ◽  
Marek's Disease Virus ◽  
Tumor Formation ◽  
Marek's Disease ◽  
Economic Losses ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus of chickens that causes lymphomas in various organs. Most MDV genes are conserved among herpesviruses, while others are unique to MDV and may contribute to pathogenesis and/or tumor formation. High transcript levels of the MDV-specific genes MDV082, RLORF11 and SORF6 were recently detected in lytically infected cells; however, it remained elusive if the respective proteins are expressed and if they play a role in MDV pathogenesis. In this study, we first addressed if these proteins are expressed by inserting FLAG tags at their N- or C- terminus. We could demonstrate that among the three genes tested, MDV082 is the only gene that encodes a protein and is expressed very late in MDV plaques in vitro. To investigate the role of this novel MDV082 protein in MDV pathogenesis, we generated a recombinant virus that lacks expression of the MDV082 protein. Our data revealed that the MDV082 protein contributes to the rapid onset of Marek’s disease, but is not essential for virus replication, spread and tumor formation. Taken together, this study sheds light on the expression of MDV-specific genes and unravels the role of the late protein MDV082 in MDV pathogenesis. Importance Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes Marek’s disease in chickens. The virus causes immense economic losses in poultry industry due to the high morbidity and mortality, but also cost of the vaccination. MDV encodes over 100 genes that are involved in various processes of the viral lifecycle. Functional characterization of MDV genes is an essential step towards understanding the complex virus lifecycle and MDV pathogenesis. Here, we have identified a novel protein encoded by MDV082 and two potential non-coding RNAs (RLORF11 and SORF6). The novel MDV082 protein is not needed for efficient MDV replication and tumor formation. However, our data demonstrate that the MDV082 protein is involved in the rapid onset of Marek’s disease.

scholarly journals Involvement of the Oncoprotein c-Myc in Viral Telomerase RNA Gene Regulation during Marek's Disease Virus-Induced Lymphomagenesis

2007 ◽  
Vol 81 (9) ◽  
pp. 4848-4857 ◽  
Author(s):  
Marina Shkreli ◽  
Ginette Dambrine ◽  
Denis Soubieux ◽  
Emmanuel Kut ◽  
Denis Rasschaert
Keyword(s):  
Transcriptional Regulation ◽  
Disease Virus ◽  
Transcriptional Start Site ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Luciferase Reporter ◽  
Telomerase Rna ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Protein Subunit

ABSTRACT 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.

Isolation and identification of Marek’s disease virus (MDV) from feather follicle epithelium and internal organs of diseased chickens in Dakahlia Governorate, Egypt

2019 ◽  
Vol 20 (2) ◽  
pp. 6-11
Author(s):  
Aly El-Kenawy ◽  
Mohamed El-Tholoth ◽  
Emad A
Keyword(s):  
Real Time ◽  
Disease Virus ◽  
Real Time Pcr ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Field Samples ◽  
Feather Follicle ◽  
Positive Results

In the present study, a total of 16 samples including feather follicle epithelium, ovary, spleen and kidney (4 samples for each organ) were collected from diseased chicken flocks suspected to be infected with Marek’s disease virus (MDV) at Dakahlia Governorate, Egypt during the period from October 2016 to October 2017. Each sample was pooled randomly from three to five birds (90 to 360 days old). The isolation of the suspected virus from the collected samples was carried out via chorioallantoic membranes (CAMs) of 12 days old embryonated chicken eggs (ECEs). Three egg passages were carried out for each sample. Hyperimmune serum was prepared against standard MDV. MDV in both field and egg passaged samples (after 3rd passage) was identified by agar gel precipitation test (AGPT) and indirect fluorescence antibody test (IFAT). Molecular identification of virus was carried out by conventional polymerase chain reaction (PCR) and real- time PCR in four selected samples. The results revealed that 14 samples (87.5%) including 4 (100%) samples from feather follicle epithelium, ovary and kidney and 2 (50%) samples from spleen, showed positive results in virus isolation after 3rd passage. The positive results percentage by AGPT for field samples were 50% (8 out of 16 samples), while after the 3rd passage in ECEs were 37.5% (6 out of 16 samples) and the positive results percentage by IFAT for field samples were 62.5% (10 out of 16 samples), while after the 3rd passage in ECEs were 81.25 % (13 out of 16 samples). Viral nucleic acid was detected in all selected samples by conventional and real- time PCR. The results indicate that feather follicle epithelium is the best organ for MDV detection. IFAT is superior over AGPT in virus detection. Conventional and real - time PCR could be efficiently used for molecular detection of the virus.

Sign in / Sign up

Export Citation Format

Share Document