Immunological aspects of Marek’s disease virus (MDV)-induced lymphoma progression

Parcells, Mark S.; Burgess, Shane C.

doi:10.1007/978-1-4020-6729-7_11

Cited by 8 publications

(3 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There was also evidence for disturbance within the polyclonal repertoire in TCRVβ2 expressing cells ( Figure 6 ) suggesting that the blood niche for T cells was being filled by the tumor. Hence, with a circulating TCR profile dominated by a single clone, it is of little surprise that MDV-infected birds develop immune deficiency [reviewed in [71] ]. These dramatic repertoire changes would have greater impact than the reported changes in cytokine production [72] and would be immunologically catastrophic.…”

Section: Discussionmentioning

confidence: 99%

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

et al. 2011

View full text Add to dashboard Cite

Lymphoid oncogenesis is a life threatening complication associated with a number of persistent viral infections (e.g. EBV and HTLV-1 in humans). With many of these infections it is difficult to study their natural history and the dynamics of tumor formation. Marek's Disease Virus (MDV) is a prevalent α-herpesvirus of poultry, inducing CD4+ TCRαβ+ T cell tumors in susceptible hosts. The high penetrance and temporal predictability of tumor induction raises issues related to the clonal structure of these lymphomas. Similarly, the clonality of responding CD8 T cells that infiltrate the tumor sites is unknown. Using TCRβ repertoire analysis tools, we demonstrated that MDV driven CD4+ T cell tumors were dominated by one to three large clones within an oligoclonal framework of smaller clones of CD4+ T cells. Individual birds had multiple tumor sites, some the result of metastasis (i.e. shared dominant clones) and others derived from distinct clones of transformed cells. The smaller oligoclonal CD4+ cells may represent an anti-tumor response, although on one occasion a low frequency clone was transformed and expanded after culture. Metastatic tumor clones were detected in the blood early during infection and dominated the circulating T cell repertoire, leading to MDV associated immune suppression. We also demonstrated that the tumor-infiltrating CD8+ T cell response was dominated by large oligoclonal expansions containing both “public” and “private” CDR3 sequences. The frequency of CD8+ T cell CDR3 sequences suggests initial stimulation during the early phases of infection. Collectively, our results indicate that MDV driven tumors are dominated by a highly restricted number of CD4+ clones. Moreover, the responding CD8+ T cell infiltrate is oligoclonal indicating recognition of a limited number of MDV antigens. These studies improve our understanding of the biology of MDV, an important poultry pathogen and a natural infection model of virus-induced tumor formation.

show abstract

Section: Discussionmentioning

confidence: 99%

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In infected chickens, pathogenic field strains of MDV can cause a mortality of up to 100% in unvaccinated flocks; however, commercial losses due to MD are effectively controlled by the use of antigenically-related live attenuated vaccines. MD vaccines prevent tumor formation, but not super infection by virulent field strains [ 8 ]. While vaccine-induced, cell-mediated immunity plays a critical role in protection against MD and humoral immunity has a limited role in protection.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Transcriptomes and Proteomes of Serum Exosomes from Marek’s Disease Virus-Vaccinated and Protected and Lymphoma-Bearing Chickens

Neerukonda

Tavlarides-Hontz

McCarthy

et al. 2019

Genes

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…To advance the understanding of functional patterns of DNA methylation in disease resistance or susceptibility, we extended the scope of examination to 18 interested genes, which include STAT1 , CIITA , NK-lysin , CD44 , IL12 , and GH1 that the expression levels of these gene are alterable upon MDV challenge (Liu et al, 2001 ; Abdul-Careem et al, 2006 ; Parcells and Burgess, 2008 ; Sarson et al, 2008a , b ; Heidari et al, 2010 ; Thanthrige-Don et al, 2010 ). Some of the 18 genes were also chosen based on our previous temporal microarray data, which include FABP3 , HDAC9 , IL28RA , MON2 , and THBS2 (Luo et al, 2011 ; Yu et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Fluctuation Induced by Virus Infection Differs between MD-resistant and -susceptible Chickens

Luo¹,

Yu²,

Chang³

et al. 2012

Front. Gene.

View full text Add to dashboard Cite

Marek’s disease (MD) is a lymphoproliferative disease induced by Marek’s disease virus (MDV) infection. To augment vaccination measures in MD control, host genetic resistant to MD becomes obviously more and more important. To elucidate the mechanism of MD-resistance, most of researches were focused on the genetic differences between resistant and susceptible chickens. However, epigenetic features between MD resistant and susceptible chickens are poorly characterized. Using bisulfite pyrosequencing method, we found some candidate genes have higher promoter methylation in the MD-susceptible (L72) chickens than in the MD-resistant (L63) chickens. The hypermethylated genes, involved in cellular component organization, responding to stimulus, cell adhesion, and immune system process, may play important role in susceptibility to disease by deregulation of these genes. MDV infection induced the expression changes of all three methyltransferases genes (DNMT1, DNMT3a, and DNMT3b) in both lines of chickens. The DNMT1 was up-regulated in L72, whereas the DNMT3b was down-regulated in L63 at 21 dpi. Interestingly, a dynamic change of promoter methylation was observed during MDV life cycle. Some genes, including HDAC9, GH, STAT1, CIITA, FABP3, LATS2, and H2Ac, showed differential methylation behaviors between the two lines of chickens. In summary, the findings from this study suggested that DNA methylation heterogeneity and MDV infection induced methylation alterations differences existed between the two lines of chickens. Therefore, it is suggested that epigenetic mechanisms may be involved in modulating the resistance and/or susceptibility to MD in chickens.

show abstract

Immunological aspects of Marek’s disease virus (MDV)-induced lymphoma progression

Cited by 8 publications

References 177 publications

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Clonal Structure of Rapid-Onset MDV-Driven CD4+ Lymphomas and Responding CD8+ T Cells

Comparison of the Transcriptomes and Proteomes of Serum Exosomes from Marek’s Disease Virus-Vaccinated and Protected and Lymphoma-Bearing Chickens

DNA Methylation Fluctuation Induced by Virus Infection Differs between MD-resistant and -susceptible Chickens

Contact Info

Product

Resources

About