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Research in Veterinary Science Mar 2021Marek's disease virus (MDV), the causative agent of Marek's disease (MD), results in highly infectious phymatosis, lymphatic tissue hyperplasia, and neoplasia. MD is... (Review)
Review
Marek's disease virus (MDV), the causative agent of Marek's disease (MD), results in highly infectious phymatosis, lymphatic tissue hyperplasia, and neoplasia. MD is associated with high morbidity and mortality rate. Non-coding RNAs (ncRNAs) entails long non-coding RNA (lncRNA) and microRNA (miRNA). Numerous studies have reported that specific miRNAs and lncRNAs participate in multiple cellular processes, such as proliferation, migration, and tumor cell invasion. Specialized miRNAs and lncRNAs militate a similar role in MD tumor oncogenesis. Despite its growing popularity, only a few reviews are available on ncRNA in MDV tumor oncogenes. Herein, we summarized the role of the miRNAs and lncRNAs in MD tumorigenesis. Altogether, we brought forth the research issues, such as MD prevention, screening, regulatory network formation, novel miRNAs, and lncRNAs analysis in MD that needs to be explored further. This review provides a theoretical platform for the further analysis of miRNAs and lncRNAs functions and the prevention and control of MD and malignancies in domestic animals.
Topics: Animals; Carcinogenesis; Chickens; Herpesvirus 2, Gallid; Marek Disease; MicroRNAs; Poultry Diseases; RNA, Long Noncoding
PubMed: 33485054
DOI: 10.1016/j.rvsc.2021.01.007 -
Transboundary and Emerging Diseases Sep 2022Marek's disease virus (MDV), an oncogenic virus belonging to the subfamily Alphaherpesvirinae, causes Marek's disease (MD). Vaccines can control MD but cannot block the...
Marek's disease virus (MDV), an oncogenic virus belonging to the subfamily Alphaherpesvirinae, causes Marek's disease (MD). Vaccines can control MD but cannot block the viral infection; they are considered imperfect vaccines, which carry the risk of recombination. In this study, six natural recombinant MDV strains were isolated from infected chickens in commercial flocks in China. We sequenced and analysed the genetic characteristics of the isolates (HC/0803, CH/10, SY/1219, DH/1307, DH/1504 and Hrb/1504). We found that the six strains resulted from recombination between the vaccine CVI988/Rispens (CVI988) strain skeleton and the virulence strain's partial unique short region. Additionally, a pathogenicity study was performed on recombinant strains (HC/0803 and DH/1307) and reference strains (CVI988 and LHC2) to evaluate their virulence. LHC2 induced 84.6% mortality in infected chickens; however, no mortality was recorded in chickens inoculated with HC/0803, DH/1307 or CVI988. However, HC/0803 and DH/1307 induced a notable spleen enlargement, and mild thymus and bursa atrophy at 11-17 days post-challenge (dpc). The viral genome load in the HC/0803- and DH/1307-challenged chickens peaked at approximately 10 viral copies per million host cells at 17 dpc and was similar to that in LHC2-challenged chickens, but significantly higher than that of CVI988-challenged chickens. In summary, HC/0803 and DH/1307 displayed mild virulence with temporal damage to the immune organs of chicken and a higher reproduction capability than the vaccine strain CVI988. Our study provides direct evidence of the emergence of recombinant MDV strains between vaccine and virulence strains in nature. The emergence of natural recombinant strains suggests that live vaccines can act as genetic donors for genomic recombination, and recombination may be a safety concern when administering live vaccines. These findings demonstrate that recombination promotes genetic diversity and increases the complexity of disease diagnosis, prevention and control.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Marek Disease; Marek Disease Vaccines; Poultry Diseases; Virulence
PubMed: 35266322
DOI: 10.1111/tbed.14506 -
Veterinary Microbiology Jul 2017Marek's disease (MD) is a lymphoproliferative viral disease of chickens, which has been controlled through vaccination since 1969. MD vaccines protect against tumors but... (Review)
Review
Marek's disease (MD) is a lymphoproliferative viral disease of chickens, which has been controlled through vaccination since 1969. MD vaccines protect against tumors but do not provide sterilizing immunity, and thus it is generally believed that their use has contributed to increase virulence of field strains with the ability to cause MD in vaccinated chickens. Traditional methods of developing vaccines, like cell culture attenuation, have proved unsuccessful for the development of improved vaccines to protect against highly virulent MD virus (MDV) field strains. With the advent of recombinant DNA technology, it is now possible to study MDV gene function and develop rational vaccines that protect against highly pathogenic strains. In addition, the long term protection conferred by MD vaccines, their excellent safety profile, their efficacy when administered early (at hatch or in ovo), and their ability to overcome maternal antibodies, has made MDV an excellent candidate vector to protect not only against MD but also against other important viral poultry diseases. In this review we will discuss the current status of MD vaccines and their use as vector vaccines to control important viral poultry diseases.
Topics: Animals; Chickens; Herpesvirus 2, Gallid; Marek Disease; Poultry Diseases; Vaccination; Viral Vaccines; Virulence
PubMed: 28038868
DOI: 10.1016/j.vetmic.2016.11.024 -
Frontiers in Immunology 2022The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed...
The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed class I molecule with strong associations between disease resistance and MHC haplotype. For Marek's disease virus (MDV) infections of chickens, the MHC haplotype is one of the major determinants of genetic resistance and susceptibility. VALO specific pathogen free (SPF) chickens are widely used in biomedical research and vaccine production. While valuable findings originate from MDV infections of VALO SPF chickens, their MHC haplotypes and associated disease resistance remained elusive. In this study, we used several typing systems to show that VALO SPF chickens possess MHC haplotypes that include B9, B9:02, B15, B19 and B21 at various frequencies. Moreover, we associate the MHC haplotypes to MDV-induced disease and lymphoma formation and found that B15 homozygotes had the lowest tumor incidence while B21 homozygotes had the lowest number of organs with tumors. Finally, we found transmission at variable levels to all contact birds except B15/B21 heterozygotes. These data have immediate implications for the use of VALO SPF chickens and eggs in the life sciences and add another piece to the puzzle of the chicken MHC complex and its role in infections with this oncogenic herpesvirus.
Topics: Animals; Carcinogenesis; Chickens; Disease Resistance; Haplotypes; Herpesvirus 2, Gallid; Histocompatibility Antigens; Major Histocompatibility Complex; Marek Disease
PubMed: 35693787
DOI: 10.3389/fimmu.2022.908305 -
Poultry Science Aug 2021The reticuloendotheliosis virus (REV) and the Marek's disease virus (MDV) cause reticuloendotheliosis (RE) and Marek's disease (MD) in poultry, respectively. According...
The reticuloendotheliosis virus (REV) and the Marek's disease virus (MDV) cause reticuloendotheliosis (RE) and Marek's disease (MD) in poultry, respectively. According to epidemiological results obtained in our laboratory from 2010 to 2017, the positive rates of REV and MDV co-infection remained at low levels. In the present study, during the period of October 2018 to July 2020, 4 clinical cases with high morbidity (5%-20%) and mortality (2%-10%), caused by the co-infection of REV and vv+ MDV-like strains, were diagnosed and analyzed by histopathological observation, cell cultures and detection with ELISA and IFA, and the PCR and by sequencing of the isolates' genes. Sequencing and the sequence analysis on the complete genomes of the REV strains and the meq genes of the MDV strains were performed. The results, based on the complete genome, LTR, gag, pol, and env genes' nucleotide sequences of the REV strains, showed that the REV isolates and 68.0 % (17/25) of the reference strains were in a same branch, and all had a high sequence similarity (>99.0%). The similarities between the four isolates and a vv+MDV strain GX18NNM4 were very high, up to 99.3-99.8%. Also, the amino acid residuals at locations 71, 77, 80, 115, 139, 176, and 217 were all the same as A, E, Y, A, A, R, and A, respectively, in the meq gene of the four MDV isolates. In addition, the substitutes at P176R and P217A interrupted the stretches of the proline-rich repeat PPPP, indicating that these strains belonged to the vv+ MDV-like category. Our findings indicated that the more recent and frequent reemergence of REV and the subsequent co-infection with vv+ MDV-like strain has become one of the causes of the clinical outbreaks of tumors and is undoubtedly a threat to the poultry industry in southern China.
Topics: Animals; Chickens; China; Coinfection; Herpesvirus 2, Gallid; Marek Disease; Poultry Diseases; Reticuloendotheliosis virus
PubMed: 34174570
DOI: 10.1016/j.psj.2021.101099 -
Veterinary Radiology & Ultrasound : the... Jul 2023A 4-year-old chicken was presented with a history of anorexia, depression, and blindness. An ultrasound examination of the coelomic cavity was performed that revealed...
A 4-year-old chicken was presented with a history of anorexia, depression, and blindness. An ultrasound examination of the coelomic cavity was performed that revealed splenomegaly, hepatic nodules, and hypoechoic thickening of the intestinal wall. Ultrasonography of the coelomic cavity was done and revealed splenomegaly, nodular hepatic changes, and hypoechoic thickening of the intestinal wall. A diagnosis of Marek's disease was made based on the history and extension of the abdominal organ changes and confirmed by histopathology. This study describes an ultrasonographic appearance of Marek's disease in a chicken and emphasizes the importance and benefits of ultrasonography in staging the progression of Marek's disease.
Topics: Animals; Marek Disease; Chickens; Splenomegaly; Herpesvirus 2, Gallid
PubMed: 37309707
DOI: 10.1111/vru.13260 -
Journal of Virology Jan 2020Viruses may hijack glycolysis, glutaminolysis, or fatty acid β-oxidation of host cells to provide the energy and macromolecules required for efficient viral...
Viruses may hijack glycolysis, glutaminolysis, or fatty acid β-oxidation of host cells to provide the energy and macromolecules required for efficient viral replication. Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens and modulates metabolism of host cells. Metabolic analysis of MDV-infected chicken embryonic fibroblasts (CEFs) identified elevated levels of metabolites involved in glutamine catabolism, such as glutamic acid, alanine, glycine, pyrimidine, and creatine. In addition, our results demonstrate that glutamine uptake is elevated by MDV-infected cells Although glutamine, but not glucose, deprivation significantly reduced cell viability in MDV-infected cells, both glutamine and glucose were required for virus replication and spread. In the presence of minimum glutamine requirements based on optimal cell viability, virus replication was partially rescued by the addition of the tricarboxylic acid (TCA) cycle intermediate, α-ketoglutarate, suggesting that exogenous glutamine is an essential carbon source for the TCA cycle to generate energy and macromolecules required for virus replication. Surprisingly, the inhibition of carnitine palmitoyltransferase 1a (CPT1a), which is elevated in MDV-infected cells, by chemical (etomoxir) or physiological (malonyl-CoA) inhibitors, did not reduce MDV replication, indicating that MDV replication does not require fatty acid β-oxidation. Taken together, our results demonstrate that MDV infection activates anaplerotic substrate from glucose to glutamine to provide energy and macromolecules required for MDV replication, and optimal MDV replication occurs when the cells do not depend on mitochondrial β-oxidation. Viruses can manipulate host cellular metabolism to provide energy and essential biosynthetic requirements for efficient replication. Marek's disease virus (MDV), an avian alphaherpesvirus, causes a deadly lymphoma in chickens and hijacks host cell metabolism. This study provides evidence for the importance of glycolysis and glutaminolysis, but not fatty acid β-oxidation, as an essential energy source for the replication and spread of MDV. Moreover, it suggests that in MDV infection, as in many tumor cells, glutamine is used for generation of energetic and biosynthetic requirements of the MDV infection, while glucose is used biosynthetically.
Topics: Alphaherpesvirinae; Animals; Chick Embryo; Chickens; Glucose; Glutamine; Glycolysis; Herpesvirus 2, Gallid; Mardivirus; Marek Disease; Viral Proteins; Virus Replication
PubMed: 31748393
DOI: 10.1128/JVI.01680-19 -
Science China. Life Sciences Feb 2023Over the past two decades, numerous non-coding RNAs (ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses... (Review)
Review
Over the past two decades, numerous non-coding RNAs (ncRNAs) have been identified in different biological systems including virology, especially in large DNA viruses such as herpesviruses. As a representative oncogenic alphaherpesvirus, Marek's disease virus (MDV) causes an important immunosuppressive and rapid-onset neoplastic disease of poultry, namely Marek's disease (MD). Vaccinations can efficiently prevent the onset of MD lymphomas and other clinical disease, often heralded as the first successful example of vaccination-based control of cancer. MDV infection is also an excellent model for research into virally-induced tumorigenesis. Recently, great progress has been made in understanding the functions of ncRNAs in MD biology. Herein, we give a review of the discovery and identification of MDV-encoded viral miRNAs, focusing on the genomics, expression profiles, and emerging critical roles of MDV-1 miRNAs as oncogenic miRNAs (oncomiRs) or tumor suppressor genes involved in the induction of MD lymphomas. We also described the involvements of host cellular miRNAs, lincRNAs, and circRNAs participating in MDV life cycle, pathogenesis, and/or tumorigenesis. The prospects, strategies, and new techniques such as the CRISPR/Cas9-based gene editing applicable for further investigation into the ncRNA-mediated regulatory mechanisms in MDV pathogenesis/oncogenesis were also discussed, together with the possibilities of future studies on antiviral therapy and the development of new efficient MD vaccines.
Topics: Animals; Cell Transformation, Neoplastic; Chickens; Herpesvirus 2, Gallid; Lymphoma; Marek Disease; MicroRNAs
PubMed: 36617590
DOI: 10.1007/s11427-022-2258-4 -
Virulence Dec 2022Co-infection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of...
Co-infection of Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of the synergism. Here, we found that co-infection of REV and MDV increased their replication via the RIOK3-Akt pathway. Initially, we noticed that the viral titres of MDV and REV significantly increased in REV and MDV co-infected cells compared with single-infected cells. Furthermore, tandem mass tag peptide labelling coupled with LC/MS analysis showed that Akt was upregulated in REV and MDV co-infected cells. Overexpression of Akt promoted synergistic replication of MDV and REV. Conversely, inhibition of Akt suppressed synergistic replication of MDV and REV. However, PI3K inhibition did not affect synergistic replication of MDV and REV, suggesting that the PI3K/Akt pathway is not involved in the synergism of MDV and REV. In addition, we revealed that RIOK3 was recruited to regulate Akt in REV and MDV co-infected cells. Moreover, wild-type RIOK3, but not kinase-dead RIOK3, mediated Akt phosphorylation and promoted synergistic replication of MDV and REV. Our results illustrate that MDV and REV activated a novel RIOK3-Akt signalling pathway to facilitate their synergistic replication.
Topics: Animals; Chickens; Coinfection; Genetic Diseases, X-Linked; Herpesvirus 2, Gallid; Humans; Marek Disease; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Reticuloendotheliosis virus; Severe Combined Immunodeficiency; Virus Replication
PubMed: 35795905
DOI: 10.1080/21505594.2022.2096247 -
Microbial Pathogenesis Sep 2022Marek's disease virus (MDV), a highly contagious cell associated virus, is the etiological agent of Marek's disease (MD), a lymphoproliferative and neuropathic disease...
Marek's disease virus (MDV), a highly contagious cell associated virus, is the etiological agent of Marek's disease (MD), a lymphoproliferative and neuropathic disease of domestic chickens. Clinical signs of MD include transient paralysis, bursal/thymic atrophy, and T cell lymphomas. MicroRNAs (miRNAs) are short single-stranded non-coding RNAs that regulate gene expression by transcriptional suppression or mRNA degradation. Herpesviruses, including MDV, encode for miRNAs that are known to play essential roles in viral pathogenicity, oncogenesis, and evasion of immune responses. In this study, we performed miRNA sequencing in thymuses of control and MDV-infected chickens of MD-resistant (6) and susceptible (7) lines at 21 days post infection (dpi). The thymus is a lymphoid organ that undergoes severe atrophy due to MDV-induced apoptotic mediated destruction of T cells. Sequence analysis identified 658 total chicken miRNAs in the thymuses of control and MDV-infected birds of both lines. Of these, 453 were novel and 205 were known microRNAs. All novel miRNAs mapped to chicken genome with no sequence homology to existing miRNAs in the chicken miRbase. Comparative analysis between the thymuses of control and infected birds of resistant and susceptible lines identified 78 differentially expressed microRNAs that might provide insights into mechanisms of thymus atrophy.
Topics: Animals; Atrophy; Chickens; Marek Disease; MicroRNAs; T-Lymphocytes
PubMed: 35917989
DOI: 10.1016/j.micpath.2022.105688