scholarly journals Transcriptional Profiles Associated with Marek’s Disease Virus in Bursa and Spleen Lymphocytes Reveal Contrasting Immune Responses during Early Cytolytic Infection

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 354
Author(s):  
Huan Jin ◽  
Zimeng Kong ◽  
Arslan Mehboob ◽  
Bo Jiang ◽  
Jian Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Disease Virus ◽  
Expression Profiles ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Splenic Lymphocytes ◽  
Cytokines And Chemokines

Marek’s disease virus (MDV), an alpha herpes virus, causes a lymphoproliferative state in chickens known as Marek’s disease (MD), resulting in severe monetary losses to the poultry industry. Because lymphocytes of bursa of Fabricius and spleen are prime targets of MDV replication during the early cytolytic phase of infection, the immune response in bursa and spleen should be the foundation of late immunity induced by MDV. However, the mechanism of the MDV-mediated host immune response in lymphocytes in the early stage is poorly understood. The present study is primarily aimed at identifying the crucial genes and significant pathways involved in the immune response of chickens infected with MDV CVI988 and the very virulent RB1B (vvRB1B) strains. Using the RNA sequencing approach, we analyzed the generated transcriptomes from lymphocytes isolated from chicken bursa and spleen. Our findings validated the expression of previously characterized genes; however, they also revealed the expression of novel genes during the MDV-mediated immune response. The results showed that after challenge with CVI988 or vvRB1B strains, 634 and 313 differentially expressed genes (DEGs) were identified in splenic lymphocytes, respectively. However, 58 and 47 DEGs were observed in bursal lymphocytes infected with CVI988 and vvRB1B strains, respectively. Following MDV CVI988 or vvRB1B challenge, the bursal lymphocytes displayed changes in IL-6 and IL-4 gene expression. Surprisingly, splenic lymphocytes exhibited an overwhelming alteration in the expression of cytokines and cytokine receptors involved in immune response signaling. On the other hand, there was no distinct trend between infection with CVI988 and vvRB1B and the expression of cytokines and chemokines, such as IL-10, IFN-γ, STAT1, IRF1, CCL19, and CCL26. However, the expression profiles of IL-1β, IL-6, IL8L1, CCL4 (GGCL1), and CCL5 were significantly upregulated in splenic lymphocytes from chickens infected with CVI988 compared with those of chickens infected with vvRB1B. Because these cytokines and chemokines are considered to be associated with B cell activation and antigenic signal transduction to T cells, they may indicate differences of immune responses initiated by vaccinal and virulent strains during the early phase of infection. Collectively, our study provides valuable data on the transcriptional landscape using high-throughput sequencing to understand the different mechanism between vaccine-mediated protection and pathogenesis of virulent MDV in vivo.

scholarly journals A Functional MicroRNA-155 Ortholog Encoded by the Oncogenic Marek's Disease Virus

2008 ◽  
Vol 83 (1) ◽  
pp. 489-492 ◽  
Author(s):  
Yuguang Zhao ◽  
Yongxiu Yao ◽  
Hongtao Xu ◽  
Luke Lambeth ◽  
Lorraine P. Smith ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Regulatory Pathways ◽  
Lymphoid Malignancies

ABSTRACT Kaposi's sarcoma-associated herpesvirus-encoded microRNA (miRNA) MiR-K12-11 was recently shown to be a functional ortholog of miR-155, a miRNA that plays a major role in lymphoid malignancies and the modulation of immune responses. Here we show that miR-M4, encoded by the highly oncogenic Marek's disease virus of chickens, shares common targets with miR-155 and thus is also a functional ortholog of miR-155, the first one identified in an alphaherpesvirus. The observation that two distinct oncogenic herpesviruses associated with distinct types of lymphomas in different species encode functional miR-155 orthologs suggested the importance of this miRNA in regulatory pathways and the biology of lymphomagenesis.

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 MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

2009 ◽  
Vol 90 (5) ◽  
pp. 1164-1171 ◽  
Author(s):  
Luke S. Lambeth ◽  
Yongxiu Yao ◽  
Lorraine P. Smith ◽  
Yuguang Zhao ◽  
Venugopal Nair
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Disease Virus ◽  
Expression Profiles ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Tumour Cell Line ◽  
Neoplastic Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

MicroRNAs (miRNAs) are a class of short RNAs that function as post-transcriptional suppressors of protein expression and are involved in a variety of biological processes, including oncogenesis. Several recent studies have implicated the involvement of miR-221 and miR-222 in tumorigenesis as these miRNAs are upregulated in a number of cancers and affect the expression of cell cycle regulatory proteins such as the cyclin-dependent kinase (cdk) inhibitor p27Kip1. Marek's disease virus (MDV) is a highly oncogenic herpesvirus that affects poultry, causing acute neoplastic disease with lymphomatous lesions in several organs. MDV-encoded oncogenes such as Meq are directly implicated in the neoplastic transformation of T cells and have been well studied. More recently, however, the involvement of both host and virus-encoded miRNAs in the induction of MD lymphomas is being increasingly recognized. We analysed the miRNA expression profiles in the MDV-transformed lymphoblastoid cell line MSB-1 and found that endogenous miRNAs miR-221 and miR-222 were significantly upregulated. Demonstration of the conserved binding sites for these miRNAs in the chicken p27Kip1 3′-untranslated region sequence and the repression of luciferase activity of reporter constructs indicated that miR-221 and miR-222 target p27Kip1 in these cells. We also found that overexpression of miR-221 and miR-222 decreased p27Kip1 levels and that treatment with retrovirally expressed antagomiRs partially alleviated this suppression. These data show that an oncogenic herpesvirus, as in the case of many cancers, can exploit the miRNA machinery for suppressing cell cycle regulatory molecules such as p27Kip1 in the induction and progression of T-cell lymphomas.

scholarly journals Protective Effect of Avian Myelomonocytic Growth Factor in Infection with Marek’s Disease Virus

2002 ◽  
Vol 76 (3) ◽  
pp. 1062-1070 ◽  
Author(s):  
Aouatef Djeraba ◽  
Eugène Musset ◽  
John W. Lowenthal ◽  
David B. Boyle ◽  
Anne-Marie Chaussé ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Growth Factor ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
No Production ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Inos Gene

ABSTRACT Marek’s disease virus (MDV) is a herpesvirus that induces T lymphomas in chickens. The aim of this study was to assess the role of the macrophage activator chicken myelomonocytic growth factor (cMGF) in controlling MDV infection. B13/B13 chickens, which are highly susceptible to MD, were either treated with cMGF delivered via a live fowlpox virus (fp/cMGF) or treated with the parent vector (fp/M3) or were left as untreated controls. Seven days later, when challenged with the very virulent RB-1B strain of MDV, the spleens of chickens treated with fp/cMGF showed increased expression of the inducible nitric oxide synthase (iNOS) gene compared to those of control chickens and fp/M3-treated chickens. Increased iNOS gene expression was also accompanied by greater induction of gamma interferon and macrophage inflammatory protein (K203) gene expression, both possible activators of iNOS. fp/cMGF treatment also increased the number of monocytes and systemic NO production in contrast to fp/M3 treatment. Even though cMGF treatment was unable to prevent death for the chickens, it did prolong their survival time, and viremia and tumor incidence were greatly reduced. In addition, cMGF treatment improved the partial protection induced by vaccination with HVT (herpesvirus isolated from turkeys) against RB-1B, preventing 100% mortality (versus 66% with vaccination alone) and greatly reducing tumor development. Treatment with fp/M3 did not have such effects. These results suggest that cMGF may play multiple roles in protection against MD. First, it may enhance the innate immune response by increasing the number and activity of monocytes and macrophages, resulting in increased NO production. Second, it may enhance the acquired immune response, indicated by its ability to enhance vaccine efficacy.

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