scholarly journals The conservation and signatures of lincRNAs in Marek’s disease of chicken

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yanghua He ◽  
Yi Ding ◽  
Fei Zhan ◽  
Huanmin Zhang ◽  
Bo Han ◽  
...  
Keyword(s):  
T Cell ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Protein Coding ◽  
Functional Studies ◽  
Wide Range ◽  
Genetic Mechanisms ◽  
Non Coding Rnas ◽  
Computational Analyses ◽  
Chicken Model

Abstract Long intergenic non-coding RNAs (lincRNAs) associated with a number of cancers and other diseases have been identified in mammals, but they are still formidable to be comprehensively identified and characterized. Marek’s disease (MD) is a T cell lymphoma of chickens induced by Marek’s disease virus (MDV). Here, we used a MD chicken model to develop a precise pipeline for identifying lincRNAs and to determine the roles of lincRNAs in T cell tumorigenesis. More than 1,000 lincRNA loci were identified in chicken bursa. Computational analyses demonstrated that lincRNAs are conserved among different species such as human, mouse and chicken. The putative lincRNAs were found to be associated with a wide range of biological functions including immune responses. Interestingly, we observed distinct lincRNA expression signatures in bursa between MD resistant and susceptible lines of chickens. One of the candidate lincRNAs, termed linc-satb1, was found to play a crucial role in MD immune response by regulating a nearby protein-coding gene SATB1. Thus, our results manifested that lincRNAs may exert considerable influence on MDV-induced T cell tumorigenesis and provide a rich resource for hypothesis-driven functional studies to reveal genetic mechanisms underlying susceptibility to tumorigenesis.

scholarly journals LncExpDB: an expression database of human long non-coding RNAs

2020 ◽  
Vol 49 (D1) ◽  
pp. D962-D968 ◽  
Author(s):  
Zhao Li ◽  
Lin Liu ◽  
Shuai Jiang ◽  
Qianpeng Li ◽  
Changrui Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Protein Coding ◽  
Web Interfaces ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Genes Expression ◽  
Wide Range ◽  
Non Coding Rnas ◽  
User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

A T-cell antigen system of chickens: Ly-4 and Marek's disease

1977 ◽  
Vol 5 (1) ◽  
pp. 535-552 ◽  
Author(s):  
Tom L. Fredericksen ◽  
Bryan M. Longenecker ◽  
Feldzgeritta Pazderka ◽  
Douglas G. Gilmour ◽  
Royal F. Ruth
Keyword(s):  
T Cell ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Cell Antigen ◽  
Antigen System

scholarly journals Mardivirus Infection and Persistence in Feathers of a Chicken Model Harboring a Local Autoimmune Response

2020 ◽  
Vol 8 (10) ◽  
pp. 1613
Author(s):  
Gisela F. Erf ◽  
Gilles Le Pape ◽  
Sylvie Rémy ◽  
Caroline Denesvre
Keyword(s):  
Inflammatory Response ◽  
Newcastle Disease ◽  
Marek's Disease ◽  
Autoimmune Response ◽  
Marek’S Disease ◽  
Autoimmune Destruction ◽  
Strong Inflammatory Response ◽  
Destruction Of Melanocytes ◽  
Chicken Model

Herpesvirus of turkey (HVT) is commonly used as a vaccine to protect chickens against Marek’s disease. Following vaccination, HVT infects feathers where it can be detected in all chicken lines examined. Unlike the parental Brown line (BL), Smyth line (SL) chickens develop vitiligo, due to autoimmune destruction of melanocytes in feathers. Previous reports showed a strong inflammatory response in Smyth chickens’ feathers at vitiligo onset, that subsided once melanocytes were destroyed, and depigmentation was complete. Here, we questioned whether the local autoimmune response in the Smyth model influences HVT infection and persistence in feathers. For this, one-day-old SL and BL chickens were vaccinated with Newcastle disease (rHVT-ND). Vitiligo was scored and HVT loads in pigmented and non-pigmented growing feathers were quantified regularly over 20 weeks. Chickens of both lines showed moderate HVT loads in feathers. At the onset of active vitiligo, the HVT load was significantly higher in SL compared to BL feathers. However, no difference in HVT loads was noticed between pigmented and non-pigmented feathers from SL chickens. Therefore, surprisingly, the inflammatory response in feathers of SL chickens did not inhibit HVT infection and persistence, but on the contrary, temporarily promoted HVT infection in feathers.

scholarly journals Marek's Disease Virus-Encoded MicroRNA 155 Ortholog Critical for the Induction of Lymphomas Is Not Essential for the Proliferation of Transformed Cell Lines

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Yaoyao Zhang ◽  
Na Tang ◽  
Jun Luo ◽  
Man Teng ◽  
Katy Moffat ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Virus ◽  
Cell Lines ◽  
Critical Role ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
T Cell Lymphomas

ABSTRACT MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) and Marek’s disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses. IMPORTANCE Marek’s disease virus (MDV) is an alphaherpesvirus associated with Marek’s disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype.

scholarly journals Long non-coding RNAs in plants: emerging modulators of gene activity in development and stress responses

Planta ◽  
2020 ◽  
Vol 252 (5) ◽  
Author(s):  
Li Chen ◽  
Qian-Hao Zhu ◽  
Kerstin Kaufmann
Keyword(s):  
Stress Responses ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Reproductive Organs ◽  
Gene Activity ◽  
Protein Coding ◽  
Wide Range ◽  
Non Coding Rnas ◽  
Coding Potential

Abstract Main conclusion Long non-coding RNAs modulate gene activity in plant development and stress responses by various molecular mechanisms. Abstract Long non-coding RNAs (lncRNAs) are transcripts larger than 200 nucleotides without protein coding potential. Computational approaches have identified numerous lncRNAs in different plant species. Research in the past decade has unveiled that plant lncRNAs participate in a wide range of biological processes, including regulation of flowering time and morphogenesis of reproductive organs, as well as abiotic and biotic stress responses. LncRNAs execute their functions by interacting with DNA, RNA and protein molecules, and by modulating the expression level of their targets through epigenetic, transcriptional, post-transcriptional or translational regulation. In this review, we summarize characteristics of plant lncRNAs, discuss recent progress on understanding of lncRNA functions, and propose an experimental framework for functional characterization.

scholarly journals Identification of the Neoplastically Transformed Cells in Marek's Disease Herpesvirus-Induced Lymphomas: Recognition by the Monoclonal Antibody AV37

2002 ◽  
Vol 76 (14) ◽  
pp. 7276-7292 ◽  
Author(s):  
Shane C. Burgess ◽  
T. Fred Davison
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Lymphoma Cell ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Marek’S Disease ◽  
Lymphoma Cells ◽  
Transformed Cell Lines ◽  
First Time

ABSTRACT Understanding the interactions between herpesviruses and their host cells and also the interactions between neoplastically transformed cells and the host immune system is fundamental to understanding the mechanisms of herpesvirus oncology. However, this has been difficult as no animal models of herpesvirus-induced oncogenesis in the natural host exist in which neoplastically transformed cells are also definitively identified and may be studied in vivo. Marek's disease (MD) herpesvirus (MDV) of poultry, although a recognized natural oncogenic virus causing T-cell lymphomas, is no exception. In this work, we identify for the first time the neoplastically transformed cells in MD as the CD4+ major histocompatibility complex (MHC) class Ihi, MHC class IIhi, interleukin-2 receptor α-chain-positive, CD28lo/−, phosphoprotein 38-negative (pp38−), glycoprotein B-negative (gB−), αβ T-cell-receptor-positive (TCR+) cells which uniquely overexpress a novel host-encoded extracellular antigen that is also expressed by MDV-transformed cell lines and recognized by the monoclonal antibody (MAb) AV37. Normal uninfected leukocytes and MD lymphoma cells were isolated directly ex vivo and examined by flow cytometry with MAb recognizing AV37, known leukocyte antigens, and MDV antigens pp38 and gB. CD28 mRNA was examined by PCR. Cell cycle distribution and in vitro survival were compared for each lymphoma cell population. We demonstrate for the first time that the antigen recognized by AV37 is expressed at very low levels by small minorities of uninfected leukocytes, whereas particular MD lymphoma cells uniquely express extremely high levels of the AV37 antigen; the AV37hi MD lymphoma cells fulfill the accepted criteria for neoplastic transformation in vivo (protection from cell death despite hyperproliferation, presence in all MD lymphomas, and not supportive of MDV production); the lymphoma environment is essential for AV37+ MD lymphoma cell survival; pp38 is an antigen expressed during MDV-productive infection and is not expressed by neoplastically transformed cells in vivo; AV37+ MD lymphoma cells have the putative immune evasion mechanism of CD28 down-regulation; AV37hi peripheral blood leukocytes appear early after MDV infection in both MD-resistant and -susceptible chickens; and analysis of TCR variable β chain gene family expression suggests that MD lymphomas have polyclonal origins. Identification of the neoplastically transformed cells in MD facilitates a detailed understanding of MD pathogenesis and also improves the utility of MD as a general model for herpesvirus oncology.

Marek’s disease virus may interfere with T cell immunity by TLR3 signals

2014 ◽  
Vol 38 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Xuming Hu ◽  
Wencai Xu ◽  
Aijian Qin ◽  
Genghua Wu ◽  
Kun Qian ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
T Cell Immunity ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Cell Immunity

scholarly journals The genome of herpesvirus of turkeys: comparative analysis with Marek’s disease viruses

2001 ◽  
Vol 82 (5) ◽  
pp. 1123-1135 ◽  
Author(s):  
Brewster F. Kingham ◽  
Vladimır Zelnık ◽  
Juraj Kopáček ◽  
Vladimır Majerčiak ◽  
Erik Ney ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
T Cell ◽  
Nucleotide Sequence ◽  
Cell Lymphoma ◽  
Biological Properties ◽  
Marek's Disease ◽  
Marek’S Disease ◽  
Potential Significance ◽  
Internal Repeat ◽  
Herpesvirus Of Turkeys

The complete coding sequence of the herpesvirus of turkeys (HVT) unique long (UL) region along with the internal repeat regions has been determined. This allows completion of the HVT nucleotide sequence by linkage to the sequence of the unique short (US) region. The genome is approximately 160 kbp and shows extensive similarity in organization to the genomes of Marek’s disease virus serotypes 1 and 2 (MDV-1, MDV-2) and other alphaherpesviruses. The HVT genome contains 75 ORFs, with three ORFs present in two copies. Sixty-seven ORFs were identified readily as homologues of other alphaherpesvirus genes. Seven of the remaining eight ORFs are homologous to genes in MDV, but are absent from other herpesviruses. These include a gene with similarity to cellular lipases. The final, HVT-unique gene is a virus homologue of the cellular NR-13 gene, the product of which belongs to the Bcl family of proteins that regulate apoptosis. No other herpesvirus sequenced to date contains a homologue of this gene. Of potential significance is the absence of a complete block of genes within the HVT internal repeat that is present in MDV-1. These include the pp38 and meq genes, which have been implicated in MDV-1-induced T-cell lymphoma. By implication, other genes present in this region of MDV-1, but missing in HVT, may play important roles in the different biological properties of the viruses.

scholarly journals Characterization and identification of long non-coding RNAs based on feature relationship

2018 ◽  
Author(s):  
Guangyu Wang ◽  
Hongyan Yin ◽  
Boyang Li ◽  
Chunlei Yu ◽  
Fan Wang ◽  
...  
Keyword(s):  
Prior Knowledge ◽  
Large Scale ◽  
Gc Content ◽  
Training Data ◽  
Significant Advance ◽  
Protein Coding ◽  
Reading Frame ◽  
Wide Range ◽  
Non Coding Rnas ◽  
Computational Identification

ABSTRACTThe significance of long non-coding RNAs (lncRNAs) in many biological processes and diseases has gained intense interests over the past several years. However, computational identification of lncRNAs in a wide range of species remains challenging; it requires prior knowledge of well-established sequences and annotations or species-specific training data, but the reality is that only a limited number of species have high-quality sequences and annotations. Here we first characterize lncRNAs by contrast to protein-coding RNAs based on feature relationship and find that the feature relationship between ORF (open reading frame) length and GC content presents universally substantial divergence in lncRNAs and protein-coding RNAs, as observed in a broad variety of species. Based on the feature relationship, accordingly, we further present LGC, a novel algorithm for identifying lncRNAs that is able to accurately distinguish lncRNAs from protein-coding RNAs in a cross-species manner without any prior knowledge. As validated on large-scale empirical datasets, comparative results show that LGC outperforms existing algorithms by achieving higher accuracy, well-balanced sensitivity and specificity, and is robustly effective (>90% accuracy) in discriminating lncRNAs from protein-coding RNAs across diverse species that range from plants to mammals. To our knowledge, this study, for the first time, differentially characterizes lncRNAs and protein-coding RNAs based on feature relationship, which is further applied in computational identification of lncRNAs. Taken together, our study represents a significant advance in characterization and identification of lncRNAs and LGC thus bears broad potential utility for computational analysis of lncRNAs in a wide range of species.

scholarly journals Differential Virus-Specific IFN-Gamma Producing T Cell Responses to Marek’s Disease Virus in Chickens With B19 and B21 MHC Haplotypes

2022 ◽  
Vol 12 ◽  
Author(s):  
Nitish Boodhoo ◽  
Shahriar Behboudi
Keyword(s):  
T Cell ◽  
Disease Virus ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Ifn Gamma ◽  
Cell Responses

Marek’s disease virus (MDV), the etiologic agent for Marek’s disease (MD), causes a deadly lymphoproliferative disease in chickens. Causes of the well-documented association between genetically defined lines of chicken and resistance to MD remain unknown. Here, the frequencies of IFN-gamma producing pp38 and MEQ-specific T cell responses were determined in line N (B21 haplotype; MD-resistant) and line P2a (B19 haplotype, MD-susceptible) chickens after infection with vaccine and/or virulent (RB1B) strains of MDV using both standard ex vivo and cultured chIFN-gamma ELISPOT assays. Notably, MDV infection of naïve and vaccinated MD-resistant chickens induced higher frequencies of IFN-gamma producing MDV-specific T cell responses using the cultured and ex vivo ELISPOT assay, respectively. Remarkably, vaccination did not induce or boost MEQ-specific effector T cells in the susceptible chickens, while it boosted both pp38-and MEQ-specific response in resistant line. Taken together, our results revealed that there is a direct association between the magnitude of T cell responses to pp38 and MEQ of MDV antigens and resistance to the disease.

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