scholarly journals Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype

2001 ◽  
Vol 38 (2) ◽  
pp. 129-142 ◽  
Author(s):  
S. C. Burgess ◽  
B. H. Basaran ◽  
T. F. Davison
Keyword(s):  
Rank Order ◽  
Clinical Signs ◽  
Antigen Expression ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Marek’S Disease ◽  
Host Genotype ◽  
Time Line ◽  
Cell Numbers ◽  
Infiltrating Cells

Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 61 (resistant) and 15I and 72 (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 72 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 61 and 72 had a similar MLS distribution in the cytolytic phase, although scores were greater in line 72. At the time lymphomas were visible in line 72, histologic lesions in line 61 were regressing. AV37+ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37+ cell numbers increased in lines 72 and 15I but decreased in lines 61 and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4+. After this time, line 72 and 15I lesions increased in size and most cells were CD4+; line 61 and N lesions decreased in size and most cells were CD8+. In all genotypes, AV37 immunostaining was weak in lesions with many CD8+ cells, suggesting that AV37 antigen expression or AV37+ cells were controlled by CD8+ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 72 > 15I > 61 > N.

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.

scholarly journals Marek’s Disease Virus Telomeric Integration Profiles of Neoplastic Host Tissues Reveal Unbiased Chromosomal Selection and Loss of Cellular Diversity during Tumorigenesis

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1630
Author(s):  
Marla C. Glass ◽  
Justin M. Smith ◽  
Hans H. Cheng ◽  
Mary E. Delany
Keyword(s):  
Disease Virus ◽  
Temporal Dynamics ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Cell Populations ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Host Chromosome ◽  
Specific Host

The avian α-herpesvirus known as Marek’s disease virus (MDV) linearly integrates its genomic DNA into host telomeres during infection. The resulting disease, Marek’s disease (MD), is characterized by virally-induced lymphomas with high mortality. The temporal dynamics of MDV-positive (MDV+) transformed cells and expansion of MD lymphomas remain targets for further understanding. It also remains to be determined whether specific host chromosomal sites of MDV telomere integration confer an advantage to MDV-transformed cells during tumorigenesis. We applied MDV-specific fluorescence in situ hybridization (MDV FISH) to investigate virus-host cytogenomic interactions within and among a total of 37 gonad lymphomas and neoplastic splenic samples in birds infected with virulent MDV. We also determined single-cell, chromosome-specific MDV integration profiles within and among transformed tissue samples, including multiple samples from the same bird. Most mitotically-dividing cells within neoplastic samples had the cytogenomic phenotype of ‘MDV telomere-integrated only’, and tissue-specific, temporal changes in phenotype frequencies were detected. Transformed cell populations composing gonad lymphomas exhibited significantly lower diversity, in terms of heterogeneity of MDV integration profiles, at the latest stages of tumorigenesis (>50 days post-infection (dpi)). We further report high interindividual and lower intraindividual variation in MDV integration profiles of lymphoma cells. There was no evidence of integration hotspots into a specific host chromosome(s). Collectively, our data suggests that very few transformed MDV+ T cell populations present earlier in MDV-induced lymphomas (32–50 dpi), survive, and expand to become the dominant clonal population in more advanced MD lymphomas (51–62 dpi) and establish metastatic lymphomas.

scholarly journals Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic Gallid alphaherpesvirus 2 Telomere Integration in Host Birds

2018 ◽  
Vol 156 (4) ◽  
pp. 204-214 ◽  
Author(s):  
Marla C. McPherson ◽  
Hans H. Cheng ◽  
Justin M. Smith ◽  
Mary E. Delany
Keyword(s):  
Temporal Dynamics ◽  
Protective Efficacy ◽  
Marek's Disease ◽  
Host Genome ◽  
Marek’S Disease ◽  
Susceptible Genotype ◽  
Host Genotype ◽  
Host Genetics ◽  
Genome Interactions ◽  
Virus Integration

Marek's disease (MD) is an infectious disease characterized by lymphomas and high mortality in susceptible chickens. The causative and ubiquitous alpha-herpesvirus known as MD virus (MDV) integrates into host telomeres during early infection through latency, known to be an important phase for oncogenic transformation. Herein, we sought to determine the influence of vaccination and host genetics on the temporal dynamics of MDV-host genome interactions. We studied integration profiles using 2 MD vaccines that vary in protective efficacy in 2 genetic lines that differ in MD resistance/susceptibility. Virus integration of both oncogenic MDV and vaccine strains was observed in both MD susceptible and resistant birds, however, the lines differed in their dynamic telomere-integration profiles. Notably, the resistant host genotype exhibited a smaller percentage of replicating cells with the virus telomere-integrated only phenotype as compared to the susceptible genotype. Vaccination with Rispens, the most protective MD vaccine, also reduced the establishment of the virus telomere-integrated only phenotype, suggesting a significant role of the phenotype in MD lymphoma development. The effect of Rispens vaccination was most dramatic in the susceptible genotype. These results suggest important connections between vaccinal immunity, MDV telomere integration, virus-induced oncogenesis, and virus-host genome interactions in the context of host genetics and disease susceptibility.

Endothelial MHC Class II Antigen Expression and Endarteritis Associated with Marek's Disease Virus Infection in Chickens

1995 ◽  
Vol 32 (4) ◽  
pp. 403-411 ◽  
Author(s):  
M. Kariuki Njenga ◽  
C. A. Dangler
Keyword(s):  
Disease Virus ◽  
Mhc Class Ii ◽  
Antigen Expression ◽  
Class Ii ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Cd8 Cells ◽  
Class Ii Antigen

Experimental Marek's disease virus (MDV) infection in chickens was used to study the early pathogenesis of virus-induced atherosclerosis. Previous investigations using this model have reported the occurrence of atherosclerotic lesions after approximately 7 months postinfection. In this study, a total of 75 susceptible Cornell P-line chickens were inoculated intraperitoneally with the CU-2 strain of MDV at 3 days of age and subsequently perfused for histologic examination. At 2, 4, 8, 13, and 20 weeks postinoculation, the ascending aorta and the brachiocephalic and coronary arteries were evaluated for early changes. Expression of class II major histocompatibility complex (Ia) antigen by the vascular endothelium was demonstrated by indirect immunodetection as early as 2 weeks after virus inoculation. This change was followed by significant thickening of the intimai layer associated with mononuclear cell infiltration. All the arteries examined from the MDV-infected chickens were affected. Preliminary immunohistochemical staining showed the presence of CD3+ CD4+, and CD8+ cells among the infiltrating cells. The results suggest that an immunopathologic mechanism may be involved in the early pathogenesis of MDV-induced atherosclerosis in chickens.

scholarly journals Safety and Efficacy Evaluation of Recombinant Marek’s Disease Virus with REV-LTR

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 399 ◽  
Author(s):  
Cuiping Song ◽  
Yang Yang ◽  
Jing Hu ◽  
Shengqing Yu ◽  
Yingjie Sun ◽  
...  
Keyword(s):  
Disease Virus ◽  
Clinical Signs ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Efficacy Evaluation ◽  
Live Attenuated Vaccine ◽  
Safety And Efficacy

Recently, chickens vaccinated with the CVI988/Rispens vaccine showed increased tumor incidence. Moreover, many strains of Marek’s disease virus (MDV) that were naturally integrated with the long terminal repeat (LTR) of the avian reticuloendotheliosis virus (REV) have been isolated, which means it is necessary to develop a new vaccine. In this study, two LTR sequences were inserted into Rispens to construct a recombinant MDV (rMDV). Then, the safety and efficacy of rMDV were evaluated separately in chickens. The growth rate curves showed that the insertion of REV-LTR into MDV enabled a faster replication in vitro than Rispens. Chickens immunized with high or repeated dose rMDV had no MD clinical signs. Further, no tumor, tissue lesions, or evident pathological changes were observed in the chicken organs. Polymerase chain reaction (PCR) and virus isolation revealed that rMDV had the ability to spread horizontally to non-immunized chickens and had no impact on the environment. After five passages in chickens, there were no obvious lesions, and the LTR insertion was stable. There were also no deletions or mutations, which indicates that rMDV is safe in chickens. In addition, rMDV has an advantage over Rispens against vvMDV Md5 at low doses. All results demonstrate that the transgenic strain of rMDV with REV-LTR can be used as a live attenuated vaccine candidate.

Sign in / Sign up

Export Citation Format

Share Document