Marek's Disease Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4
            <sup>+</sup>
            CD25
            <sup>+</sup>
            T Cells

Engel, Annemarie T.; Selvaraj, Ramesh K.; Kamil, Jeremy P.; Osterrieder, Nikolaus; Kaufer, Benedikt B.

doi:10.1128/jvi.00556-12

Cited by 71 publications

(90 citation statements)

References 40 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A, ⌬a-like). It was shown recently that deletion of most of the IR L was completely restored by homologous recombination events during viral DNA replication after only two passages in cell culture (13). We therefore hypothesized that the deletion of the a-like sequence would also be repaired within a few passages in CEC.…”

Section: Generation and Characterization Of V⌬a-like Virusmentioning

confidence: 97%

“…Recombinant viruses were reconstituted by transfection of CEC with purified bacterial artificial chromosome (BAC) DNA using CaPO 4 transfection (13,16,24,25). Virus was propagated on CEC for 2 to 4 passages, and infected cells were stored in liquid nitrogen.…”

Section: Cells and Virusesmentioning

confidence: 99%

“…In addition, vTR can promote tumor formation independently of its presence in the telomerase complex (10). Several other factors are also involved in lymphomagenesis, including the MDV chemokine viral interleukin-8 (vIL-8) and MDV-encoded microRNAs (miRNAs) (4,(12)(13)(14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

Greco

Fester

Engel

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

Marek's disease virus (MDV) is a cell-associated alphaherpesvirus that causes generalized polyneuritis and T-cell lymphomas in chickens. MDV is able to integrate its genome into host telomeres, but the mechanism of integration is poorly understood. The MDV genome harbors two arrays of telomeric repeats (TMR) at the ends of its linear genome: multiple telomeric repeats (mTMR), with a variable number of up to 100 repeats, and short telomeric repeats (sTMR), with a fixed number of 6 repeats. The mTMR have recently been shown to play an important role in MDV integration and tumor formation; however, the functions of the sTMR have remained unknown. In this study, we demonstrate that deletion of the sTMR in the MDV genome abrogates virus replication, while extensive mutation of the sTMR does not, indicating that the presence of the sTMR but not the sTMR sequence itself is important. Furthermore, we generated a panel of truncation mutants to determine the minimal length of the sTMR and observed a direct correlation between sTMR length and MDV replication. To address the role of sTMR in MDV replication, integration, and tumorigenesis, sTMR sequences were replaced by a scrambled repeated sequence (vsTMR_mut). vsTMR_mut replicated comparably to parental and revertant viruses in vitro. In vivo, however, a significant reduction in disease and tumor incidence was observed in chickens infected with vsTMR_mut that also correlated with a reduced number of viral integration sites in tumor cells. Taken together, our data demonstrate that the sTMR play a central role in MDV genome replication, pathogenesis, and MDV-induced tumor formation. IMPORTANCE Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes high economic losses in the poultry industry. MDV integrates its genetic material into host telomeres, a process that is crucial for efficient tumor formation.The MDV genome harbors two arrays of telomeric repeats (TMR) at the ends of its linear genome that are identical to host telomeres and that are termed mTMR and sTMR. mTMR have been recently shown to be involved in MDV integration, while the functions of sTMR remain unknown. Here, we demonstrate that the presence and length of sTMR sequence, but not the exact nucleotide sequence, are crucial for MDV replication. Furthermore, the sTMR contribute to the high integration frequency of MDV and are important for MDV pathogenesis and tumor formation. As a number of herpesviruses harbor arrays of telomeric repeats (TMR), MDV serves as a model to determine the role of the herpesvirus TMR in replication, integration, and pathogenesis.

show abstract

Section: Generation and Characterization Of V⌬a-like Virusmentioning

confidence: 97%

Section: Cells and Virusesmentioning

confidence: 99%

See 1 more Smart Citation

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

Greco

Fester

Engel

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…(B) eGFP expression in a cell tumor removed from a necropsied MDV (eGFP-GLuc2A-VP22)-infected chicken. Tumors from visceral organs were collected at necropsy and cultured using standard protocols (15). Pictures in the upper panel show photographs of the induced solid tumors, especially in the kidneys of both parental-and eGFP-GLuc2A-VP22-infected chickens.…”

Section: Fig 3 (A)mentioning

confidence: 99%

“…According to the current paradigm, MDV belongs to a unique class of viruses that rely exclusively on cell-to-cell transmission (12)(13)(14)(15). In contrast, it has been reported that infectious, cell-free MDVs are produced in feather follicle epithelial cells, and these may directly participate in viral transmission in chickens (16,17).…”

mentioning

confidence: 99%

A Virulent Bioluminescent and Fluorescent Dual-Reporter Marek's Disease Virus Unveils an Alternative Spreading Pathway in Addition to Cell-to-Cell Contact

Harmache

2014

J Virol

View full text Add to dashboard Cite

Marek's disease virus (MDV) is a growing threat for the poultry industry. Unfortunately, despite successful vaccination against the disease, MDV remains in circulation within vaccinated flocks, leading to the selection of increasingly virulent pathotypes. Detailed knowledge of the virus biology and the host-virus interaction is required to improve the vaccine efficiency. In the present study, I engineered an original, dual-reporter MDV to track and quantify virus replication in vitro and in vivo.

show abstract

Neoplastic Diseases

Nair¹,

Gimeno²,

Dunn³

et al. 2019

Diseases of Poultry

View full text Add to dashboard Cite

Marek's Disease Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4 ⁺ CD25 ⁺ T Cells

Cited by 71 publications

References 40 publications

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

A Virulent Bioluminescent and Fluorescent Dual-Reporter Marek's Disease Virus Unveils an Alternative Spreading Pathway in Addition to Cell-to-Cell Contact

Neoplastic Diseases

Contact Info

Product

Resources

About

Marek's Disease Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4 + CD25 + T Cells

Cited by 71 publications

References 40 publications

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

Role of the Short Telomeric Repeat Region in Marek's Disease Virus Replication, Genomic Integration, and Lymphomagenesis

A Virulent Bioluminescent and Fluorescent Dual-Reporter Marek's Disease Virus Unveils an Alternative Spreading Pathway in Addition to Cell-to-Cell Contact

Neoplastic Diseases

Contact Info

Product

Resources

About

Marek's Disease Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4 ⁺ CD25 ⁺ T Cells