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 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 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.

Immune Responses in Cecal Tonsils of Marek's Disease Virus–Infected Chickens

2015 ◽  
Vol 59 (2) ◽  
pp. 213-226 ◽  
Author(s):  
Mohammad Heidari ◽  
Scott D. Fitzgerald ◽  
Huanmin Zhang
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

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.

Analysis of immune responses in chickens infected with Marek's disease virus

2009 ◽  
Vol 128 (1-3) ◽  
pp. 224
Author(s):  
Rika Kano ◽  
Shiro Murata ◽  
Tsukasa Okada ◽  
Satoru Konnai ◽  
Misao Onuma ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease

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.

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