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Virology Feb 2023Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and...
Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and apoptosis during the Marek's Disease Virus (MDV) latency in vaccinated chickens. Vaccinated chickens were inoculated with the MD5 strain and were dissected at different time points. The viremia occurs in the spleen and thymus during the latency period of MD5 infection, however, lesions can be observed in the liver tissue. The latency-associated early gene of MDV, i.e., ICP4, was highly expressed in the spleen and thymus during the early latency. Compared with the early cytolytic stage, apoptosis of splenocytes was remarkably downregulated in the latency period. This study suggests that MDV latency could occur in the spleen and thymus in vaccinated chickens and there is a negative correlation between the MDV latency and apoptosis of spleen. MDV latency can resist the apoptosis of spleen.
Topics: Animals; Marek Disease; Chickens; Viremia; Herpesvirus 2, Gallid; Apoptosis
PubMed: 36696868
DOI: 10.1016/j.virol.2023.01.003 -
Veterinarni Medicina Nov 2023Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The...
Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek's disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical.
PubMed: 38163046
DOI: 10.17221/75/2023-VETMED -
Epidemics Jun 2019The industrialization of farming has had an enormous impact. To most, this impact is viewed solely in the context of productivity, but the denser living conditions and...
The industrialization of farming has had an enormous impact. To most, this impact is viewed solely in the context of productivity, but the denser living conditions and shorter rearing periods of industrial livestock farms provide pathogens with an ideal opportunity to spread and evolve. For example, the industrialization of poultry farms drove the Marek's disease virus (MDV) to evolve from a mild paralytic syndrome to a highly contagious, globally prevalent, deadly disease. Fortunately, the economic catastrophe that would occur from MDV evolution is prevented through the widespread use of live imperfect vaccines that limit disease symptoms, but fail to prevent transmission. Unfortunately, the continued rollout of such imperfect vaccines is steering MDV evolution towards even greater virulence, and the ability to evade vaccine protection. Thus, there is a need to investigate alternative economically viable control measures for their ability to inhibit MDV spread and evolution. In what follows we examine the economic viability of standard husbandry practices for their ability to inhibit the spread of both virulent MDV and very virulent MDV throughout an industrialized egg farm. To do this, we parameterize a MDV transmission model and calculate the loss in egg production due to MDV. We find that MDV strain and the cohort duration have the greatest influence on both disease burden and egg production. Additionally, our findings show that for long cohort durations, conventional cages result in the least per capita loss in egg production due to MDV infection, while Aviary systems perform best over shorter cohort durations. Finally, we find that the least per capita loss in egg production for flocks infected with the more virulent MDV strains occurs when cohort durations are sufficiently short. These results highlight the important decisions that managers will face when implementing new hen husbandry practices.
Topics: Animals; Chickens; Eggs; Food Industry; Marek Disease; Virulence
PubMed: 30745241
DOI: 10.1016/j.epidem.2019.01.004 -
Avian Pathology : Journal of the W.V.P.A Oct 2018Marek's disease (MD), characterised by rapid-onset lymphoid tumours, immunosuppression and paralysis, is one of the most widespread economically important diseases of...
Marek's disease (MD), characterised by rapid-onset lymphoid tumours, immunosuppression and paralysis, is one of the most widespread economically important diseases of poultry world-wide. Caused by the highly contagious Marek's disease virus, control of MD is mainly achieved through vaccination with live attenuated vaccines, although improvements in genetic resistance have also been an important component of disease control. Despite the overall success of the vaccination policy in controlling MD in the last 40 years, continuous evolution of virulence and emergence of hypervirulent pathotypes remains the major challenge for sustainable control of this disease.
Topics: Animals; Health Policy; Marek Disease; Marek Disease Vaccines; Poultry; Vaccination
PubMed: 29882420
DOI: 10.1080/03079457.2018.1484073 -
Vaccine Nov 2015Viral infections are associated with production losses in many animal production industries. Important examples of this are Marek's disease (MD) and bovine respiratory... (Review)
Review
Viral infections are associated with production losses in many animal production industries. Important examples of this are Marek's disease (MD) and bovine respiratory disease (BRD) which are significant issues in the chicken and cattle industries, respectively. Viruses play key roles in MD and BRD development and consequently have also been utilised in vaccination strategies to control these diseases. Despite the widespread availability and use of vaccines to control these diseases both are still major issues for their respective industries. Here the dual role of members of viruses from the family Herpesviridae in causation and control of MD and BRD will be discussed. The technologies that may lead to the development of improved vaccines to provide more sustainable control of MD and BRD will also be identified.
Topics: Animals; Cattle; Chickens; Drug Discovery; Herpesviridae; Herpesvirus Vaccines; Infectious Bovine Rhinotracheitis; Marek Disease; Veterinary Medicine
PubMed: 26387436
DOI: 10.1016/j.vaccine.2015.09.028 -
Frontiers in Immunology 2022The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek's disease (MD) which...
The major histocompatibility complex (MHC) haplotype is one of the major determinants of genetic resistance and susceptibility of chickens to Marek's disease (MD) which is caused by an oncogenic herpesvirus; Marek's disease virus (MDV). To determine differential functional abilities of T cells associated with resistance and susceptibility to MD, we identified immunodominant CD4+TCRvβ1 T cell epitopes within the pp38 antigen of MDV in B19 and B21 MHC haplotype chickens using an ELISPOT assay for chicken IFN-gamma. These novel pp38 peptides were used to characterize differential functional abilities of T cells as associated with resistance and susceptibility to MD. The results demonstrated an upregulation of cytokines (IL-2, IL-4, IL-10) and lymphocyte lysis-related genes (perforin and granzyme B) in an antigen specific manner using RT-PCR. In the MD-resistant chickens (B21 MHC haplotype), antigen-specific and non-specific response was highly skewed towards Th2 response as defined by higher levels of IL-4 expression as well as lymphocyte lysis-related genes compared to that in the MD-susceptible chicken line (B19 MHC haplotype). Using CD107a degranulation assay, the results showed that MDV infection impairs cytotoxic function of T cells regardless of their genetic background. Taken together, the data demonstrate an association between type of T cell response to pp38 and resistance to the disease and will shed light on our understanding of immune response to this oncogenic herpesvirus and failure to induce sterile immunity.
Topics: Animals; Antiviral Agents; Chickens; Cytokines; Epitopes, T-Lymphocyte; Granzymes; Herpesvirus 2, Gallid; Interleukin-10; Interleukin-2; Interleukin-4; Marek Disease; Perforin
PubMed: 36189228
DOI: 10.3389/fimmu.2022.973762 -
Genes Nov 2021Marek's disease (MD) was an immunosuppression disease induced by Marek's disease virus (MDV). MD caused huge economic loss to the global poultry industry, but it also...
Marek's disease (MD) was an immunosuppression disease induced by Marek's disease virus (MDV). MD caused huge economic loss to the global poultry industry, but it also provided an ideal model for studying diseases induced by the oncogenic virus. Alternative splicing (AS) simultaneously produced different isoform transcripts, which are involved in various diseases and individual development. To investigate AS events in MD, RNA-Seq was performed in tumorous spleens (TS), spleens from the survivors (SS) without any lesion after MDV infection, and non-infected chicken spleens (NS). In this study, 32,703 and 25,217 AS events were identified in TS and SS groups with NS group as the control group, and 1198, 1204, and 348 differently expressed (DE) AS events (-value < 0.05 and FDR < 0.05) were identified in TS vs. NS, TS vs. SS, SS vs. NS, respectively. Additionally, Function enrichment analysis showed that ubiquitin-mediated proteolysis, p53 signaling pathway, and phosphatidylinositol signaling system were significantly enriched (-value < 0.05). Small structural variations including SNP and indel were analyzed based on RNA-Seq data, and it showed that the TS group possessed more variants on the splice site region than those in SS and NS groups, which might cause more AS events in the TS group. Combined with previous circRNA data, we found that 287 genes could produce both circular and linear RNAs, which suggested these genes were more active in MD lymphoma transformation. This study has expanded the understanding of the MDV infection process and provided new insights for further analysis of resistance/susceptibility mechanisms.
Topics: Alternative Splicing; Animals; Chickens; Gene Expression Profiling; Mardivirus; Marek Disease; Polymorphism, Single Nucleotide; RNA; RNA Splice Sites; RNA, Circular; Signal Transduction; Spleen
PubMed: 34946806
DOI: 10.3390/genes12121857 -
Veterinary Medicine (Auckland, N.Z.) 2022Marek's disease virus is a devastating infection, causing high morbidity and mortality in chickens in Ethiopia.
BACKGROUND
Marek's disease virus is a devastating infection, causing high morbidity and mortality in chickens in Ethiopia.
METHODS
The current study was conducted from March to November, 2021 with the general objective of performing antemortem and postmortem, isolation, and molecular detection of Marek's disease virus from outbreak cases in southwestern Ethiopia. Accordingly, based on outbreak information reported from the study sites namely, Bedelle, Yayo, and Bonga towns in southwestern Ethiopia, 50 sick chickens were sampled. The backyard and intensive farming systems of chickens were included in the sampling and priorities were given for chickens that showed clinical signs that are characteristics of Marek's disease.
RESULTS
By clinical examinations, paralysis of legs and wings, gray eye, loss of weight, difficulty in breathing, and depression were recorded on all chickens sampled for this study and death of diseased chickens was observed. In addition, enlargement of the spleen and gross lesions of the liver and heart were recorded during postmortem examination. The death of infected chickens was observed in both vaccinated and non-vaccinated flocks. Out of 50 pooled feather follicle samples, Marek's disease virus was isolated from 14/50 (28%) by cell culture method and out of six tissue samples, the virus was isolated from 5/6(83.30%). By Real time polymerization chain reaction technique, which was targeted to detect the Meq gene, Marek's disease virus was detected from 18/50 feather follicles which accounts for 36% of sampled chickens.
CONCLUSION
In general, current study showed that the circulating Marek's disease virus in southwestern Ethiopia was caused by the oncogenic Gallid herpesvirus-2 (Serotype-1). Further research on molecular characterization of revolving virus in current and other regions is recommended for effective control of the disease through vaccination.
PubMed: 36199365
DOI: 10.2147/VMRR.S376795 -
Journal of Virology May 2022Circular RNAs (circRNAs) are a recently rediscovered class of functional noncoding RNAs that are involved in gene regulation and cancer development. Next-generation...
Circular RNAs (circRNAs) are a recently rediscovered class of functional noncoding RNAs that are involved in gene regulation and cancer development. Next-generation sequencing approaches identified circRNA fragments and sequences underlying circularization events in virus-induced cancers. In the present study, we performed viral circRNA expression analysis and full-length sequencing in infections with Marek's disease virus (MDV), which serves as a model for herpesvirus-induced tumorigenesis. We established inverse PCRs to identify and characterize circRNA expression from the repeat regions of the MDV genome during viral replication, latency, and reactivation. We identified a large variety of viral circRNAs through precise mapping of full-length circular transcripts and detected matching sequences with several viral genes. Hot spots of circRNA expression included the transcriptional unit of the major viral oncogene encoding the Meq protein and the latency-associated transcripts (LATs). Moreover, we performed genome-wide bioinformatic analyses to extract back-splice junctions from lymphoma-derived samples. Using this strategy, we found that circRNAs were abundantly expressed from the same key virulence genes. Strikingly, the observed back-splice junctions do not follow a unique canonical pattern, compatible with the U2-dependent splicing machinery. Numerous noncanonical junctions were observed in viral circRNA sequences characterized from and infections. Given the importance of the genes involved in the transcription of these circRNAs, our study contributes to our understanding and complexity of this deadly pathogen. Circular RNAs (circRNAs) were rediscovered in recent years both in physiological and pathological contexts, such as in cancer. Viral circRNAs are encoded by at least two human herpesviruses, the Epstein Barr virus and the Kaposi's Sarcoma-associated herpesvirus, both associated with the development of lymphoma. Marek's disease virus (MDV) is a well-established animal model to study virus-induced lymphoma but circRNA expression has not been reported for MDV yet. Our study provided the first evidence of viral circRNAs that were expressed at key steps of the MDV lifecycle using genome-wide analyses of circRNAs. These circRNAs were primarily found in transcriptional units that corresponded to the major MDV virulence factors. In addition, we established a bioinformatics pipeline that offers a new tool to identify circular RNAs in other herpesviruses. This study on the circRNAs provided important insights into major MDV virulence genes and herpesviruses-mediated gene dysregulation.
Topics: Animals; Chickens; Epstein-Barr Virus Infections; Genome-Wide Association Study; Herpesvirus 2, Gallid; Lymphoma; Marek Disease; Oncogene Proteins, Viral; RNA, Circular; RNA, Untranslated; Virulence
PubMed: 35412345
DOI: 10.1128/jvi.00321-22 -
PLoS Biology Mar 2020Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it...
Many livestock and human vaccines are leaky because they block symptoms but do not prevent infection or onward transmission. This leakiness is concerning because it increases vaccination coverage required to prevent disease spread and can promote evolution of increased pathogen virulence. Despite leakiness, vaccination may reduce pathogen load, affecting disease transmission dynamics. However, the impacts on post-transmission disease development and infectiousness in contact individuals are unknown. Here, we use transmission experiments involving Marek disease virus (MDV) in chickens to show that vaccination with a leaky vaccine substantially reduces viral load in both vaccinated individuals and unvaccinated contact individuals they infect. Consequently, contact birds are less likely to develop disease symptoms or die, show less severe symptoms, and shed less infectious virus themselves, when infected by vaccinated birds. These results highlight that even partial vaccination with a leaky vaccine can have unforeseen positive consequences in controlling the spread and symptoms of disease.
Topics: Animals; Chickens; Feathers; Herpesvirus 2, Gallid; Host-Pathogen Interactions; Marek Disease; Vaccination; Viral Load; Viral Vaccines; Virulence; Virus Shedding
PubMed: 32134914
DOI: 10.1371/journal.pbio.3000619