Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Research Note: Characterization of S-Meq containing the deletion in Meq protein's transactivation domain in a Marek's disease virus strain in Japan.

ABSTRACT: Marek's disease virus (MDV) causes malignant lymphomas in chickens (Marek's disease; MD). Although MD has caused significant economic losses to the poultry industry, currently, its occurrence in the field is effectively controlled by vaccination. However, the genetic characteristics of MDV strains have changed, and the poultry industry has experienced MD outbreaks in vaccinated chickens because of enhanced virulence. Meq, an oncoprotein of MDV, is a key transcription factor correlated with the tumorigenesis in MD. Animal experiments using recombinant MDV revealed that distinct polymorphisms in Meq affect the virulence of MDV strains. Meq containing an insertion or deletion is present in some MDV strains. In the 2010s, field strains that encode Meq containing the deletion (S-Meq) were reported. In this study, we characterized the genetic features of S-Meq detected in a Japanese MDV strain and analyzed its transactivation activity to investigate S-Meq's protein function. S-Meq lacked 41 amino acids, and the deletion was at the same position as those observed in other countries. In addition, S-Meq exhibited higher transactivation activity than Meq from other MDV strains circulating in Japan. These results suggest that the deletion in the transactivation domain may enhance the Meq protein's function. Further investigation is needed to clarify whether the deletion in the transactivation domain of Meq affects MDV's virulence.

SUBMITTER: Murata S

PROVIDER: S-EPMC8531842 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Nuclear localization and dynamic properties of the Marek's disease virus oncogene products Meq and Meq/vIL8.

Project description:Marek's disease virus (MDV) is an avian herpesvirus that causes T-cell lymphomas and immune suppression in susceptible chickens. At least one gene product, MDV Eco Q-encoded protein (Meq), is essential for the oncogenicity of MDV. Alternative splicing permits the meq gene to give rise to two major transcripts encoding proteins designated Meq and Meq/vIL8. Meq is a basic leucine zipper protein capable of modulating transcription. The Meq/vIL8 protein retains a modified leucine zipper, along with the mature receptor-binding portion of vIL8, but lacks the domain of Meq responsible for transcriptional modulation. In this report, we describe studies using fusions between either Meq or Meq/vIL8 and fluorescent proteins to characterize the distribution and properties of these products in chicken embryo fibroblasts (CEFs). Meq and Meq/vIL8 both localized to the nucleoplasm, nucleoli, and Cajal bodies of transfected cells. Similar distributions were found for fluorescent fusion proteins and native Meq or Meq/vIL8. Fluorescence recovery after photobleaching and photoactivatable green fluorescent protein revealed that Meq exhibited mobility properties similar to those of other transcription factors, while Meq/vIL8 was far less mobile. In addition, fluorescence resonance energy transfer studies indicated the formation of Meq/vIL8 homodimers in CEFs. Time lapse studies revealed the coordinated elimination of a portion of Meq and Meq/vIL8 from the nucleus. Our data provide new insight regarding the dynamic cellular properties of two forms of a herpesvirus-encoded oncoprotein and suggest that these forms may have fundamentally different functions in MDV-infected cells.

| S-EPMC1346918 | biostudies-literature

Genetic characterization of a Marek's disease virus strain isolated in Japan.

Project description:BackgroundMarek's disease virus (MDV) causes malignant lymphomas in chickens (Marek's disease, MD). MD is currently controlled by vaccination; however, MDV strains have a tendency to develop increased virulence. Distinct diversity and point mutations are present in the Meq proteins, the oncoproteins of MDV, suggesting that changes in protein function induced by amino acid substitutions might affect MDV virulence. We previously reported that recent MDV isolates in Japan display distinct mutations in Meq proteins from those observed in traditional MDV isolates in Japan, but similar to those in MDV strains isolated from other countries.MethodsTo further investigate the genetic characteristics in Japanese field strains, we sequenced the whole genome of an MDV strain that was successfully isolated from a chicken with MD in Japan. A phylogenetic analysis of the meq gene was also performed.ResultsPhylogenetic analysis revealed that the Meq proteins in most of the Japanese isolates were similar to those of Chinese and European strains, and the genomic sequence of the Japanese strain was classified into the Eurasian cluster. Comparison of coding region sequences among the Japanese strain and MDV strains from other countries revealed that the genetic characteristics of the Japanese strain were similar to those of Chinese and European strains.ConclusionsThe MDV strains distributed in Asian and European countries including Japan seem to be genetically closer to each other than to MDV strains from North America. These findings indicate that the genetic diversities of MDV strains that emerged may have been dependent on the different vaccination-based control approaches.

| S-EPMC7684920 | biostudies-literature

Deletion of the Viral Thymidine Kinase in a Meq-Deleted Recombinant Marek's Disease Virus Reduces Lymphoid Atrophy but Is Less Protective.

Project description:Marek's disease (MD) is a ubiquitous disease of domesticated chickens and its etiologic agent is the Gallid alphaherpesvirus 2 (GaHV-2), also known as Marek's disease virus (MDV). MD is currently controlled by vaccination using live attenuated strains of MDV (e.g., CVI988/Rispens), non-pathogenic serotypes of MDV (GaHV-3), or non-pathogenic strains of the related Melagrid alphaherpesvirus 1 (MeHV-1). One attractive strategy for the production of new vaccine strains is a recombinant MDV attenuated by the deletion of the major viral oncogene meq. However, meq-deleted variants of MDV cause atrophy of the bursa and thymus in maternal antibody-negative chickens, and the resulting immunosuppression makes them unsuitable. Herein we detail our attempt to mitigate the lymphoid atrophy caused by meq-deleted MDV by further attenuation of the virus through ablation of the viral thymidine kinase (tk) gene. We demonstrate that ablation of the viral tk from the meq-deleted virus rMd5B40/Δmeq resulted in a virus attenuated for replication in vitro and which spared chickens from atrophy of the lymphoid organs in vivo. When the rMd5B40/Δmeq/Δtk/GFP was used as a vaccine it was protective against challenge with the vv+MDV strain 686, but the protection was less than that provided by the CVI988/Rispens vaccine.

| S-EPMC8779792 | biostudies-literature

Sequence analysis of Meq oncogene among Indian isolates of Marek's disease herpesvirus.

Project description:Marek's disease (MD), caused by Marek's disease virus (MDV), is a highly contagious neoplastic disease of chicken that can be prevented by vaccination. However, in recent years many cases of vaccine failure have been reported worldwide as chickens develop symptoms of MD in spite of proper vaccination. Distinct polymorphism and point mutations in Meq gene of MDV have been reported to be associated with virulence and oncogenicity. The present study was carried out with the objective to isolate and characterize field isolates of MDV on the basis of Meq gene. Twenty five samples of suspected cases of MD were collected and processed for virus isolation in duck embryo fibroblast (DEF) primary culture where 28% (7 of 25) samples showed characteristic cytopathic effects of MDV in the form of plaques and syncytia. Additional evidence of presence of MDV in these samples was confirmed by PCR. To analyze diversity in all seven isolates of MDV, a polymorphism study was carried out by cloning and sequencing of full length of Meq gene (1020 bp). Sequence homology of 7 isolates with 23 reference strains showed 98.10-99.40% similarity in nucleotide and 95.90-98.50% similarity in amino acid sequences. Six isolates revealed 5 repeat sequences of 4 prolines (PPPP) whereas, one isolate revealed only 4 repeats. In phylogenetic analysis, these isolates formed a separate cluster showing close relatedness to the Chinese isolates. The study indicates a high mutation rate in field isolates of MDV that may be probable cause of vaccination failure.

| S-EPMC5006142 | biostudies-literature

Positive Selection Drives Rapid Evolution of the meq Oncogene of Marek's Disease Virus.

Project description:Marek's disease (MD), caused by Marek's disease virus (MDV), a poultry-borne alphaherpesvirus, is a devastating disease of poultry causing an estimated annual loss of one billion dollars to poultry producers, worldwide. Despite decades of control through vaccination, MDV field strains continue to emerge having increased virulence. The evolutionary mechanism driving the emergence of this continuum of strains to increased MDV virulence, however, remains largely enigmatic. Increase in MDV virulence has been associated with specific amino acid changes within the C-terminus domain of Mareks's EcoRI-Q (meq)-encoded oncoprotein. In this study, we sought to determine whether the meq gene has evolved adaptively and whether past vaccination efforts have had any significant effect on the reduction or increase of MDV diversity over time. Our analysis suggests that meq is estimated to be evolving at a much faster rate than most dsDNA viruses, and is comparable with the evolutionary rate of RNA viruses. Interestingly, most of the polymorphisms in meq gene appear to have evolved under positive selection and the time of divergence at the meq locus coincides with the period during which the poultry industry had undergone transitions in management practices including the introduction and widespread use of live attenuated vaccines. Our study has revealed that the decades-long use of vaccines did not reduce MDV diversity, but rather had a stimulating effect on the emergence of field strains with increased genetic diversity until the early 2000s. During the years 2004-2005, there was an abrupt decline in the genetic diversity of field isolates followed by a recovery from this bottleneck in the year 2010. Collectively, these data suggest that vaccination seems to not have had any effect on MDV eradication, but rather had a stimulating effect on MDV emergence through adaptation.

| S-EPMC5035050 | biostudies-literature

Diversity of Meq gene from clinical Marek's disease virus infection in Saudi Arabia.

Project description:AimThe aim of this study was to demonstrate the genomic features of Meq gene of Marek's disease virus (MDV) recently circulating in Saudi Arabia (SA).Materials and methodsTwo poultry flocks suffering from mortalities and visceral tumors were presented to the Veterinary Teaching Hospital, King Faisal University, SA. Subjected to different diagnostic procedures: Case history, clinical signs, and necropsy as well as polymerase chain reaction followed by Meq gene sequence analysis.ResultsCase history, clinical signs, and necropsy were suggestive of MDV infection. The Meq gene was successfully detected in liver and spleen of infected chickens. A 1062 bp band including the native Meq ORF in addition to a 939 bp of S-Meq (short isoform of Meq) were amplified from Saudi 01-13 and Saudi 02-13, respectively. The nucleotide and deduced amino acids sequences of the amplified Meq genes of both Saudi isolates showed distinct polymorphism when compared with the standard USA virulent isolates Md5 and GA. The sequence analysis of the S-Meq gene showed a 123 bp deletion representing 41 amino acids between two proline-rich areas without any frameshift. The Meq gene encoded four repeats of proline-rich repeats (PRRs sequences), whereas the S-Meq contains only two PRRs. Interestingly, the phylogenetic analysis revealed that both of SA MDV isolates are closely related to the MDV strains from Poland.ConclusionThe two MDV isolates contain several nucleotide polymorphisms resulting in distinct amino acid substitutions. It is suggested that migratory and wild birds, as well as world trading of poultry and its by-products, have a great contribution in the transmission of MDVs overseas.

| S-EPMC4937047 | biostudies-literature

Marek's disease virus encodes MicroRNAs that map to meq and the latency-associated transcript.

Project description:MicroRNAs (miRNAs) are a class of small (approximately 22-nucleotide) regulatory molecules that block translation or induce degradation of target mRNAs. These have been identified in a wide range of organisms, including viruses. In particular, the oncogenic gammaherpesviruses Kaposi's sarcoma herpesvirus and Epstein-Barr virus encode miRNAs that could potentially regulate either viral or host genes. To determine if Marek's disease virus (MDV), an oncogenic alphaherpesvirus of chickens, encodes miRNAs, we isolated small RNAs from MDV-infected chicken embryo fibroblasts (CEF) and used the 454 Life Sciences sequencing technology to obtain the sequences of 13,679 candidate host and viral small RNAs. Eight miRNAs were found, five of which flank the meq oncogene and three that map to the latency-associated transcript (LAT) region of the genome. The meq gene is unique to pathogenic serotypes of MDV and is transcriptionally active during latency and transformation, and the LAT region of the MDV genome is antisense to the immediate-early gene ICP4. Secondary structure analysis predicted that the regions flanking the miRNAs could form hairpin precursors. Northern blot analysis confirmed expression of all miRNAs in MDV-infected CEF, MDV-induced tumors, and MDV lymphoblastoid cell lines. We propose that the MDV miRNAs function to enable MDV pathogenesis and contribute to MDV-induced transformation of chicken T cells.

| S-EPMC1563840 | biostudies-literature

Genes and pathways involved in cellular transformation by Marek's disease oncoprotein Meq

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-07-01 | GSE48454 | GEO

Transcriptional profiling of mEq-dependent genes in Marek's disease resistant and susceptible inbred chicken lines.

Project description:Marek's disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marek's disease virus (MDV). Understanding the genes and biological pathways that confer MD genetic resistance should lead towards the development of more disease resistant commercial poultry flocks or improved MD vaccines. MDV mEq, a bZIP transcription factor, is largely attributed to viral oncogenicity though only a few host target genes have been described, which has impeded our understanding of MDV-induced tumorigenesis. Given the importance of mEq in MDV-induced pathogenesis, we explored the role of mEq in genetic resistance to MDV. Using global transcriptome analysis and cells from MD resistant or susceptible birds, we compared the response to infection with either wild type MDV or a nononcogenic recombinant lacking mEq. As a result, we identified a number of specific genes and pathways associated with either MD resistance or susceptibility. Additionally, integrating prior information from ChIP-seq, microarray analysis, and SNPs exhibiting allele-specific expression (ASE) in response to MDV infection, we were able to provide evidence for 24 genes that are polymorphic within mEq binding sites are likely to account for gene expression in an allele-specific manner and potentially for the underlying genetic differences in MD incidence.

| S-EPMC3804455 | biostudies-literature

The oncogenic microRNA OncomiR-21 overexpressed during Marek's disease lymphomagenesis is transactivated by the viral oncoprotein Meq.

Project description:Gallid herpesvirus 2 (GaHV-2) is an oncogenic herpesvirus that causes T lymphoma in chicken. GaHV-2 encodes a basic leucine zipper (bZIP) protein of the AP-1 family, Meq. Upon formation of homo- or heterodimers with c-Jun, Meq may modulate the expression of viral and cellular genes involved in lymphomagenesis. GaHV-2 also encodes viral microRNAs (miRNAs) involved in latency and apoptosis escape. However, little is known about cellular miRNA deregulation during the development of GaHV-2-associated lymphoma. We determined the cellular miRNA expression profiles of chickens infected with a very virulent strain (RB-1B) or a vaccine strain (CVI988) or noninfected. Among the most deregulated cellular miRNAs, we focused our efforts on gga-miR-21, which is upregulated during GaHV-2 infection. We mapped the gga-miR-21 promoter to the 10th intron of the TMEM49 gene and found it to be driven by AP-1- and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. Finally, gga-miR-21 was overexpressed only during infection with a very virulent strain (RB-1B) and not during infection with a nononcogenic strain (CVI988), providing further evidence for its role in GaHV-2 lymphomagenesis. Our data therefore suggest an additional role for Meq in GaHV-2-mediated lymphomagenesis through the induction of miR-21 expression.

| S-EPMC3536390 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data