-
Viruses Feb 2023Marek's disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic disease in chickens known as...
Marek's disease virus (MDV), a highly cell-associated oncogenic α-herpesvirus, is the etiological agent of T cell lymphomas and neuropathic disease in chickens known as Marek's disease (MD). Clinical signs of MD include neurological disorders, immunosuppression, and lymphoproliferative lymphomas in viscera, peripheral nerves, and skin. Although vaccination has greatly reduced the economic losses from MD, the molecular mechanism of vaccine-induced protection is largely unknown. To shed light on the possible role of T cells in immunity induced by vaccination, we vaccinated birds after the depletion of circulating T cells through the IP/IV injection of anti-chicken CD4 and CD8 monoclonal antibodies, and challenged them post-vaccination after the recovery of T cell populations post-treatment. There were no clinical signs or tumor development in vaccinated/challenged birds with depleted CD4 or CD8 T cells. The vaccinated birds with a combined depletion of CD4 and CD8 T cells, however, were severely emaciated, with atrophied spleens and bursas. These birds were also tumor-free at termination, with no virus particles detected in the collected tissues. Our data indicated that CD4 and CD8 T lymphocytes did not play a critical role in vaccine-mediated protection against MDV-induced tumor development.
Topics: Animals; Marek Disease; CD8-Positive T-Lymphocytes; Chickens; Lymphoma; Herpesvirus 2, Gallid; Viral Vaccines
PubMed: 36992357
DOI: 10.3390/v15030648 -
Animals : An Open Access Journal From... Jul 2020Marek's disease virus is an economically important avian herpesvirus that causes tumors and immunosuppression in chickens and turkeys. The virus, disease, and vaccines... (Review)
Review
Marek's disease virus is an economically important avian herpesvirus that causes tumors and immunosuppression in chickens and turkeys. The virus, disease, and vaccines have been known for more than 50 years, but as knowledge gaps still exists, intensive research is still ongoing. The understanding of MDV complexity can provide scientific insight in topics that cannot be experimented in humans, providing a unique model that is dually useful for the benefit of the poultry industry and for studying general herpesvirology. The present review presents the following topics: the MDV biology, the vaccine's and virulent virus' peculiar presence in feathers, protection by vaccination. In addition, two relatively behind the scenes topics are reviewed; first, the meq MDV oncogene and its recent implication in molecular epidemiology and in the MDV virulence determination, and second, the functionality of conformational epitopes of the MDV immunodominant protein, glycoprotein B. Our studies were particular, as they were the only ones describing three-dimensional MDV gB oligomers. MDV gB (glycoprotein B) continuous and discontinuous epitopes were shown to possess distinctive neutralization activities. In contrast, the significance of oligomerization of the viral membrane proteins for the creation of discontinuous epitopes in other herpesviruses was explored extensively.
PubMed: 32751762
DOI: 10.3390/ani10081319 -
Data in Brief Dec 2016The data described are related to the article entitled "Sequence Analysis of Meq oncogene among Indian isolates of Marek׳s Disease Herpesvirus" M. Gupta, D. Deka,...
The data described are related to the article entitled "Sequence Analysis of Meq oncogene among Indian isolates of Marek׳s Disease Herpesvirus" M. Gupta, D. Deka, Ramneek, 2016. Seven meq genes of Ludhiana Marek׳s disease virus (MDV) field isolates were PCR amplified by using proof reading Platinum Pfx DNA polymerase enzyme, sequenced and then analyzed for the distinct polymorphisms and point mutations. The sequences were named as LDH 1758, LDH 2003, LDH 2483, LDH 2614, LDH 2700, LDH 2929 and LDH 3262. At this point, their deduced Meq amino acid sequences were compared with GenBank available already sequenced meq genes worldwide in their deduced amino acid form to study their identity/similarity with each other.
PubMed: 27656677
DOI: 10.1016/j.dib.2016.08.052 -
The Journal of General Virology Jul 2018Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs...
Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45-MHC-Isplenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.
Topics: Animals; Antibodies, Viral; Carcinogenesis; Chickens; Female; Herpesvirus 1, Gallid; Herpesvirus 2, Gallid; Immunity, Humoral; Immunologic Deficiency Syndromes; Lymphoma; Marek Disease; MicroRNAs; RNA, Viral; Species Specificity; Viral Vaccines; Virulence
PubMed: 29767614
DOI: 10.1099/jgv.0.001076 -
Viruses Jan 2019Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and integrates its genome into the telomeres of latently infected cells. MDV encodes...
Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and integrates its genome into the telomeres of latently infected cells. MDV encodes two proteins, UL12 and UL29 (ICP8), that are conserved among herpesviruses and could facilitate virus integration. The orthologues of UL12 and UL29 in herpes simplex virus 1 (HSV-1) possess exonuclease and single strand DNA-binding activity, respectively, and facilitate DNA recombination; however, the role of both proteins in the MDV lifecycle remains elusive. To determine if UL12 and/or UL29 are involved in virus replication, we abrogated their expression in the very virulent RB-1B strain. Abrogation of either UL12 or UL29 resulted in a severe impairment of virus replication. We also demonstrated that MDV UL12 can aid in single strand annealing DNA repair, using a well-established reporter cell line. Finally, we assessed the role of UL12 and UL29 in MDV integration and maintenance of the latent virus genome. We could demonstrate that knockdown of UL12 and UL29 does not interfere with the establishment or maintenance of latency. Our data therefore shed light on the role of MDV UL12 and UL29 in MDV replication, DNA repair, and maintenance of the latent virus genome.
Topics: Animals; Cell Line; Chickens; DNA Repair; DNA Replication; DNA, Viral; Genome, Viral; Herpesvirus 2, Gallid; Marek Disease; Recombination, Genetic; Viral Proteins; Virus Latency; Virus Replication
PubMed: 30696089
DOI: 10.3390/v11020111 -
Poultry Science Jun 2023Marek's disease (MD) is a lymphoproliferative neoplastic disease caused by Marek's disease virus (MDV). Previous studies have showed that DNA methylation was involved in...
Integrated analysis of methylation profiles and transcriptome of Marek's disease virus-infected chicken spleens reveal hypomethylation of CD4 and HMGB1 genes might promote Marek's disease tumorigenesis.
Marek's disease (MD) is a lymphoproliferative neoplastic disease caused by Marek's disease virus (MDV). Previous studies have showed that DNA methylation was involved in MD development, but systematic studies are still lacking. Herein, we performed whole genome bisulfite sequencing (WGBS) and RNA-seq in MDV-infected tumorous spleens (IN), noninfected spleens (NoIN), and survivor (SUR) spleens of chickens to identify the genes playing important roles in MD tumor transformation. We generated the first genome-wide DNA methylation profile of MDV-infected, noninfected, and survivor chickens. Combined the WGBS and RNA-Seq, we found that the expression of 25% differential expression genes (DEGs) were significantly correlated with methylation of CpG sites in their gene bodies or promoters. Further, we focused on the DEGs with differentially methylated regions (DMRs) on genes' body and promoter, and it showed the expression of 60% DEGs were significantly correlated with methylation of CpG sites in DMRs. Finally, we identified 8 genes, including CD4, CTLA4, DTL, HMGB1, LGMN, NUP210, RAD52, and ZAP70, and their expression was negatively correlated with methylation of DMRs in their promoters in both IN vs. NoIN and IN vs. SUR. These 8 genes showed specifically high expression in IN groups and clustered in module turquoise analyzed by WGCNA. Out of 8 genes, CD4 and HMGB1 were drop in QTLs associated with MD resistance. Thus, we overexpressed the 2 genes to simulate their high expression in the IN group and found they significantly promoted MDCC-MSB-1 cell proliferation, which revealed they might play promoting roles in MD tumorigenesis in IN due to their high expression induced by hypomethylation.
Topics: Animals; Marek Disease; Chickens; Transcriptome; Spleen; DNA Methylation; HMGB1 Protein; Herpesvirus 2, Gallid; Carcinogenesis; Neoplasms
PubMed: 37043960
DOI: 10.1016/j.psj.2023.102594 -
Frontiers in Veterinary Science 2022Marek's disease, an economically important disease of chickens caused by virulent serotype 1 strains of the Marek's disease virus (MDV-1), is effectively controlled in...
Rapid, Sensitive, and Species-Specific Detection of Conventional and Recombinant Herpesvirus of Turkeys Vaccines Using Loop-Mediated Isothermal Amplification Coupled With a Lateral Flow Device Readout.
Marek's disease, an economically important disease of chickens caused by virulent serotype 1 strains of the Marek's disease virus (MDV-1), is effectively controlled in the field by live attenuated vaccine viruses including herpesvirus of turkeys (HVT)-both conventional HVT (strain FC126) and, in recent years, recombinant HVT viruses carrying foreign genes from other avian viruses to protect against both Marek's disease and other avian viral diseases. Testing to monitor and confirm successful vaccination is important, but any such test must differentiate HVT from MDV-1 and MDV-2, as vaccination does not prevent infection with these serotypes. End-point and real-time PCR tests are widely used to detect and differentiate HVT, MDV-1 and MDV-2 but require expensive specialist laboratory equipment and trained operators. Here, we developed and validated two tube-based loop-mediated isothermal amplification tests coupled with detection by lateral flow device readout (LAMP-LFD): an HVT-specific test to detect both conventional and recombinant HVT strains, and a second test using novel LAMP primers to specifically detect the Vaxxitek® recombinant HVT. Specificity was confirmed using DNA extracted from virus-infected cultured cells, and limit of detection was determined using plasmid DNA carrying either the HVT or Vaxxitek® genome. The LAMP-LFD tests accurately detected all HVT vaccines, or Vaxxitek® only, in crude DNA as well as purified DNA extracted from field samples of organs, feathers, or poultry house dust that were confirmed positive for HVT by real-time PCR. These LAMP-LFD tests have potential for specific, rapid, simple, and inexpensive detection of HVT vaccines in the field.
PubMed: 35812862
DOI: 10.3389/fvets.2022.873163 -
Poultry Science Sep 2020Marek's disease virus (MDV) causes T-cell lymphoma in susceptible chicken and is also related to an imbalance of the lipid metabolism. Adiponectin is a circulatory...
Marek's disease virus (MDV) causes T-cell lymphoma in susceptible chicken and is also related to an imbalance of the lipid metabolism. Adiponectin is a circulatory cytokine secreted from adipose tissue and exerts critical metabolic functions. Although the associations between adiponectin and diseases, including lipid disorder and noncardiac vascular diseases, have been reported, little is known about the relationship between MDV infection and adiponectin. Here, we challenged white Leghorns from Marek's disease (MD)-susceptible and MD-resistant lines with MDV at 7 D of age and then explored the body weight and plasma lipoprotein levels at 21 D after MDV infection. Meanwhile, adiponectin and the expression of its receptors were detected using quantitative real-time PCR and Western blot. The results showed that MDV infection induced body weight loss in all the experimental birds. Meanwhile, the concentrations of total cholesterol and high-density lipoprotein were lower after the infection, although there was no significant difference (P > 0.05). However, the infection did not affect adiponectin circulating levels in plasma. MD-susceptible birds had much lower plasma adiponectin than MD-resistant birds (P < 0.01). In abdominal fat, there was no significant difference in adiponectin mRNA level. Still, we observed a significant decrease in adiponectin protein concentration, as well as adipoR1 and adipoR2, at both mRNA and protein levels in the infected compared with the noninfected MD-susceptible chickens. In the spleen, MDV infection significantly reduced the adiponectin mRNA expression but increased the protein in MD-susceptible chickens, which decreased both adipoR1 mRNA expression and protein levels. Also interestingly, the adipoR1 mRNA expression level was significantly increased in MD-susceptible chickens in the liver after MDV infection. All findings in the present study provided interesting insights into adiponectin metabolism in chickens after MDV infection, which helps to advance the understanding of lipid metabolism in response to herpesvirus infection.
Topics: Adiponectin; Animals; Chickens; Gene Expression Profiling; Herpesvirus 2, Gallid; Lipid Metabolism; Marek Disease; Receptors, Adiponectin
PubMed: 32867969
DOI: 10.1016/j.psj.2020.06.004 -
Journal of Virological Methods Jan 2019Extracellular vesicles (EVs) is a collective term used to refer microparticles, exosomes, and apoptotic bodies produced by a variety of cells and released into... (Comparative Study)
Comparative Study
Comparison of exosomes purified via ultracentrifugation (UC) and Total Exosome Isolation (TEI) reagent from the serum of Marek's disease virus (MDV)-vaccinated and tumor-bearing chickens.
Extracellular vesicles (EVs) is a collective term used to refer microparticles, exosomes, and apoptotic bodies produced by a variety of cells and released into interstitial spaces and bodily fluids. Serum exosomes can serve as invaluable biomarkers, containing m/miRNAs, lipids, and proteins, indicative of various conditions. There are currently limited studies on the characterization and mutual consensus of biomarker profiles of serum exosomes purified by different methods. Here we compared the advantages and disadvantages of two commonly used serum exosome purification procedures including ultracentrifugation (UC) and Total Exosome Isolation (TEI) reagent, by analyzing exosome size distribution, concentration, morphology and miRNA expression profiles. Serum was obtained from Marek's disease virus (MDV)-infected chickens that were either vaccinated against Marek's disease (MD), and thus protected, or unvaccinated and bearing MDV-induced tumors. Nanoparticle tracking analysis (NTA) and Transmission Electron Microscopy (TEM) were performed to evaluate particle size, concentration, and morphological integrity, respectively. Our results indicate that the size distribution of particles purified by either procedure is consistent with that of exosomes (30-150 nm). TEI reagent generated higher yields and co-isolated additional EV populations that are slightly larger (∼180 nm). Based on the miRNA expression profiles from a previous high throughput sequencing experiment of exosome small RNAs, we selected six cellular and four MDV1 miRNAs, to validate their expression in UC- and TEI-purified exosomes. miRNA expression profiles displayed relative correlation between the two procedures, but distinctive differences were observed in abundance with TEI-purified exosomes showing higher miRNA expression consistent with higher yield than those purified by UC. TEI-purified exosomes from vaccinated chickens exhibited greater expression of tumor suppressor miRNA, gga-mir-146b and least expression of oncomiR, gga-mir-21 compared to those obtained from tumor-bearing chickens. We propose that gga-mir-146 and -21 can serve as serum exosome biomarkers for vaccine-induced protection and MD tumors respectively.
Topics: Animals; Biomarkers; Chickens; Circulating MicroRNA; Exosomes; Herpesvirus 2, Gallid; Marek Disease; Marek Disease Vaccines; Poultry Diseases; Reagent Kits, Diagnostic; Ultracentrifugation
PubMed: 30316797
DOI: 10.1016/j.jviromet.2018.10.004 -
Biologicals : Journal of the... Jan 2019Globally, vaccines are used to prevent and control the menace of infectious diseases in livestock with some reported to be inadvertently contaminated with extraneous...
Globally, vaccines are used to prevent and control the menace of infectious diseases in livestock with some reported to be inadvertently contaminated with extraneous agents (EAs). With the aim of screening and characterizing for some selected EAs, 44 live viral poultry vaccines were randomly selected based on availability. The vaccines comprised 14 manufacturers in 10 different countries including Nigeria were screened by Polymerase Chain Reaction. In 9% (4/44) of the vaccines, contamination with only avian leukosis virus (ALV) subgroup J (ALV-J) was recorded. Other exogenous ALV subgroups, chicken infectious anemia and infectious laryngotracheitis viruses were absent. The EAs was found in infectious bursal disease (n = 1), Fowlpox (n = 2) and Mareks disease (n = 1) vaccines. Phylogenetic analysis of the ALV-J env gene showed clustering with contemporary group I and II. The result underscores the importance of screening vaccines to avoid the introduction and spread of EAs that could pose a threat to poultry production.
Topics: Animals; Avian Leukosis; Avian Leukosis Virus; Drug Contamination; Gene Products, env; Nigeria; Phylogeny; Polymerase Chain Reaction; Poultry; Poultry Diseases; Vaccines, Attenuated; Viral Vaccines
PubMed: 30454953
DOI: 10.1016/j.biologicals.2018.11.003