scholarly journals Detection of p53 mutation and serum monitoring alert caused by Marek's disease virus

2020 ◽  
Author(s):  
Huixia Zhang ◽  
Mengda Liu ◽  
Hui Zhang ◽  
Shengliang Cao ◽  
Yue Li ◽  
...  
Keyword(s):  
Human Cancer ◽  
Point Mutations ◽  
Suppressor Gene ◽  
P53 Mutation ◽  
Marek's Disease ◽  
Economic Losses ◽  
Control Group ◽  
Neoplastic Disease ◽  
Marek’S Disease ◽  
Infected Chicken

Abstract Background: Marek’s disease as a chicken neoplastic disease, brings huge economic losses to the global poultry industry. The tumor suppressor gene, wild type P53, plays a key role in blocking cell cycle, promoting apoptosis and maintaining stability of genome. However, the p53 could become an oncogene from a tumor inhibitory role, if a mutation happened. Results: The mutation rate of p53 was 60 percent in experimentally and naturally infected chickens. The mutations included point-mutations and deletions, and mostly located in the DNA-binding domain. The mutated P53 can be expressed in tumors of various tissues in an infected chicken. They accumulated in cytoplasm due to the loss of nuclear localization function. Unlike the researches on human cancer, the concentration of P53 serum of MD infected chicken was significantly lower than control group. Conclusions: The p53 mutations were relevant with the development of MD. Detecting the concertation of P53 and P53 antibody in serum could be helpful for diagnosis and monitor of MD.

scholarly journals Detection of p53 mutation and serum monitoring alert caused by Marek’s disease virus in poultry

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Huixia Zhang ◽  
Mengda Liu ◽  
Hui Zhang ◽  
Shengliang Cao ◽  
Yue Li ◽  
...  
Keyword(s):  
Human Cancer ◽  
Point Mutations ◽  
Suppressor Gene ◽  
Marek's Disease ◽  
Economic Losses ◽  
Control Group ◽  
Neoplastic Disease ◽  
Mutant P53 ◽  
Marek’S Disease ◽  
Infected Chicken

Abstract Background Marek’s disease (MD) is a chicken neoplastic disease, which brings huge economic losses to the global poultry industry. The wild type p53, a tumor suppressor gene, plays a key role in blocking cell cycle, promoting apoptosis, and maintaining the stability of the genome. However, the mutant p53 losses its tumor inhibitory role and become an oncogene when a mutation has happened. Results The mutation rate of p53 was 60% in the experimentally and naturally infected chickens. The mutations included point-mutations and deletions, and mostly located in the DNA-binding domain. The mutated p53 was expressed in various tumor tissues in an infected chicken. The mutant P53 proteins were notably accumulated in the cytoplasm due to the loss in the function of nuclear localization. Unlike the study on human cancer, the concentrations of P53 in the serums of MD infected chicken were significantly lower than the control group. Conclusions The p53 mutations were apparent in the development of MD. P53 and P53 antibody level in serum could be a useful marker in the diagnosis and surveillance of MD.

scholarly journals Detection of p53 mutation and serum monitoring alert caused by Marek's disease virus

2020 ◽  
Author(s):  
Huixia Zhang ◽  
Mengda Liu ◽  
Hui Zhang ◽  
Shengliang Cao ◽  
Yue Li ◽  
...  
Keyword(s):  
Point Mutation ◽  
Suppressor Gene ◽  
P53 Mutation ◽  
Marek's Disease ◽  
Economic Losses ◽  
Neoplastic Disease ◽  
Marek’S Disease ◽  
Infected Chicken ◽  
Serum Monitoring ◽  
Risk Of Cancer

Abstract Background Marek’s disease (MD), as a chicken neoplastic disease, brings huge economic losses to the global poultry industry. The tumor suppressor gene, wild type P53 plays a key role in blocking cell cycle, promoting apoptosis and maintaining stability of genome. The p53 function could change to that of an oncogene from a tumor inhibitory role, if a mutation happened. It will increase risk of cancer incidence. Results It was found that the mutation rate of p53 was 60 percent in experimentally infected and naturally infected chickens. The mutations included point-mutation and deletions, and mostly located in the DNA-binding domain. The most common point mutation happened in five sites, which were 651, 786, 828, 864 and 879 respectively. The mutated P53 can be expressed in tumors of various tissues in an infected chicken because of the lengthening of the half-life of mutated P53. Due to the loss of nuclear localization function, most of mutated P53 were expressed in cytoplasm. The concentration of P53 was decrease in serum of MD infected chicken. Conclusions Results of the current study suggested that p53 mutations with different types were common in MD, and most of mutated P53 were expressed in cytoplasm. Detecting the concertation of P53 and P53 antibody in serum could be helpful for diagnosis and monitor of MD.

scholarly journals Exploration of Alternative Splicing (AS) Events in MDV-Infected Chicken Spleens

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1857
Author(s):  
Lulu Wang ◽  
Gang Zheng ◽  
Yiming Yuan ◽  
Ziyi Wang ◽  
Changjun Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Infection Process ◽  
Marek's Disease ◽  
Individual Development ◽  
Control Group ◽  
P Value ◽  
Marek’S Disease ◽  
Rna Seq ◽  
Infected Chicken ◽  
Structural Variations

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 (p-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 (p-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.

scholarly journals Genetic evolution of Marek's disease virus in vaccinated poultry farms

2021 ◽  
pp. 1342-1353
Author(s):  
Nahed Yehia ◽  
Hemat S. El-Sayed ◽  
Sabry E. Omar ◽  
Ahmed Erfan ◽  
Fatma Amer
Keyword(s):  
Disease Virus ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Economic Losses ◽  
Neoplastic Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Gallid Herpesvirus 2 ◽  
Highly Virulent ◽  
Meq Gene

Background and Aim: The Marek's disease virus (MDV) is a neoplastic disease causing serious economic losses in poultry production. This study aimed to investigate MDV occurrence in poultry flocks in the Lower Egypt during the 2020 breakout and genetically characterized Meq, gL, and ICP4 genes in field strains of MDV. Materials and Methods: Forty samples were collected from different breeds from eight Egyptian governorates in 2020. All flocks had received a bivalent vaccine (herpesvirus of turkey FC-126 + Rispens CVI988). However, weight loss, emaciation, reduced egg production, paralysis, and rough/raised feather follicles occurred. Samples were collected from feather follicles, liver, spleen, and nerve tissue for diagnosis by polymerase chain reaction. MDV genetic characterization was then performed by sequencing the Meq, gL, and ICP4 genes of five positive samples representing different governorates and breeds. Results: A total of 28 samples were positive for MDV field strains, while two were related to MDV vaccinal strains. All samples tested negative for ALV (A, B, C, D, and J) and REV. Phylogenetic analysis of the Meq gene of sequenced samples revealed that all MDVs were related to the highly virulent European viruses (Gallid herpesvirus 2 ATE and PC12/30) with high amino acid (A.A.) identity 99.2-100%. Alternatively, there was low A.A. identity with the vaccine strains CVI988 and 3004 (up to 82.5%). These results indicate that further investigation of the efficacy of current Egyptian vaccines is required. The Egyptian strains also harbor a specific mutation, allowing clustering into two subgroups (A and B). By mutation analysis of the Meq gene, the Egyptian viruses in our study had R101K, P217A, and E263D mutations present in all Egyptian viruses. Furthermore, R176A and T180A mutations specific to our strains contributed to the high virulence of highly virulent strains. There were no mutations of the gL or ICP4 genes. Conclusion: Further studies should evaluate the protection contributed by current vaccines used in Egypt.

scholarly journals Genome-wide characterization of copy number variations in the host genome in genetic resistance to Marek's disease using next generation sequencing

2020 ◽  
Author(s):  
Hao Bai ◽  
Yanghua He ◽  
Yi Ding ◽  
Huanmin Zhang ◽  
Jilan Chen ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Copy Number ◽  
Marek's Disease ◽  
Neoplastic Disease ◽  
Marek’S Disease ◽  
Next Generation ◽  
Qrt Pcr ◽  
Genome Wide ◽  
A Genome ◽  
Generation Sequencing

Abstract Background: Marek’s disease (MD) is a highly neoplastic disease primarily affecting chickens, and remains as a chronic infectious disease that threatens the poultry industry. Copy number variation (CNV) has been examined in many species and is recognized as a major source of genetic variation that directly contributes to phenotypic variation such as resistance to infectious diseases. Two highly inbred chicken lines 63 (MD-resistant) and 72 (MD-susceptible), as well as their F1 generation and six recombinant congenic strains (RCSs) with varied susceptibility to MD, are considered as ideal models to identify the complex mechanisms of genetic and molecular resistance to MD.Results: In the present study, to unravel the potential genetic mechanisms underlying resistance to MD, we performed a genome-wide CNV detection using next generation sequencing on the inbred chicken lines with the assistance of CNVnator. As a result, a total of 1,649 CNV regions (CNVRs) were successfully identified after merging all the nine datasets, of which 90 CNVRs were overlapped across all the chicken lines. Within these shared regions, 1,360 harbored genes were identified. In addition, 55 and 44 CNVRs with 62 and 57 harbored genes were specifically identified in line 63 and 72, respectively. Bioinformatics analysis showed that the nearby genes were significantly enriched in 36 GO terms and 6 KEGG pathways including JAK/STAT signaling pathway. Ten CNVRs (nine deletions and one duplication) involved in 10 disease-related genes were selected for validation by using qRT-PCR, all of which were successfully confirmed. Finally, qRT-PCR was also used to validate two deletion events in line 72 that were definitely normal in line 63. One high-confidence gene, IRF2 was identified as the most promising candidate gene underlying resistance and susceptibility to MD in view of its function and overlaps with data from previous study.Conclusions: Our findings provide valuable insights for understanding the genetic mechanism of resistance to MD and the identified gene and pathway could be considered as the subject of further functional characterization.

scholarly journals Exon 5 of the p53 gene is a target for deletions in ovarian cancer

1998 ◽  
Vol 44 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Katerina Angelopoulou ◽  
Michael A Levesque ◽  
Dionyssios Katsaros ◽  
Rob Shipman ◽  
Eleftherios P Diamandis
Keyword(s):  
Ovarian Cancer ◽  
Human Cancer ◽  
Insertion Site ◽  
Point Mutations ◽  
Pcr Amplification ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Protein Product ◽  
The Other ◽  
Chromosome 17

Abstract Missense point mutations, leading to inactivation of the p53 tumor suppressor gene product, are currently the most frequent alterations in human cancer. Little, however, is known about small intragenic deletions or insertions occurring in this locus of chromosome 17. We have analyzed 56 primary ovarian tumors for the presence of such abnormalities. The analysis was based on multiplex PCR amplification of exons 1 through 11 of the p53 gene and fragment analysis of the generated PCR products. Mutations were detected in 14% (8 of 56) of the tumors. Deletions were much more prevalent than insertions (seven vs one). Six of the deletions and the insertion affected exon 5, and the other deletion was in exon 7. Two deletions and the insertion did not disrupt the reading frame; the protein product was expressed in the tumor at high concentrations in all three cases. The other five deletions generated a frameshift, which is predicted to result in the production of a truncated protein product. In the case of the deletions, a 2–5-bp repeat was present close to the detected deletion, whereas the insertion duplicated the sequence immediately upstream of the insertion site. Overall our findings indicate that small intragenic p53 deletions/insertions are not rare events in ovarian cancer, and that p53 exon 5 is the target in the vast majority (88%) of the cases.

Isolation of a Field Marek’s Disease Virus with Acute Oncogenicity from Tibetan Chickens in China and Sequence Analysis of Oncogenic Genes

2011 ◽  
Vol 343-344 ◽  
pp. 538-544
Author(s):  
Ming Xing Tian ◽  
Rui Deng ◽  
Yang Zhao ◽  
Min Li ◽  
San Jie Cao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Challenge Test ◽  
Point Mutations ◽  
Repeated Sequence ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Specific Pathogen ◽  
Meq Gene

A field Marek’s disease virus (MDV), named as BY strain, was firstly isolated from Tibetan chickens in Sichuan province, China, by method of co-cultivation of the lymphocytes with duck embryo fibroblasts (DEF). Analysis of the oncogenic genes showed that there were 2 copies of 132-bp repeated sequence in long terminal repeat of the BY strain, The nucleotide and amino acid sequence identities of Meq gene of BY strain with other prevalent MDV strains in China were 97.6-100.0% and 98.8-100.0%, respectively, and some point mutations assumed to be relevant to the oncogenecity of MDV also existed in the Meq gene of BY strain. The result of animal challenge test on specific-pathogen-free (SPF) chickens showed lymphomas may occur in a variety of organs as early as 18 days post challenge, and the rate of tumor occurrences and mortalities reached to 73.33% and 66.67% in HVT immunized chickens, respectively. In conclusion, an MDV strain charac-terized of acute oncogenicity was isolated from Tibetan chickens in China, though there were no obvious difference between the oncogenic genes of this strain and other virulent MDV strains isolated in China in recent years.

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.

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