Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors

Pauker, Viktoria Isabella; Bertzbach, Luca D.; Hohmann, Angelika; Kheimar, Ahmed; Teifke, Jens Peter; Mettenleiter, Thomas C.; Karger, Axel; Kaufer, Benedikt B.

doi:10.1128/msphere.00569-18

Cited by 11 publications

(9 citation statements)

References 70 publications

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“…The latter hypothesis is consistent with observation on other oncogenic viruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus [47]. However, CD30 overexpression in MDV-induced tumors could not be confirmed in follow-up studies [48].…”

Section: Plos Pathogenssupporting

confidence: 85%

Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance

et al. 2020

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Modified-live herpesvirus vaccines are widely used in humans and animals, but field strains can emerge that have a higher virulence and break vaccinal protection. Since the introduction of the first vaccine in the 1970s, Marek’s disease virus overcame the vaccine barrier by the acquisition of numerous genomic mutations. However, the evolutionary adaptations in the herpesvirus genome responsible for the vaccine breaks have remained elusive. Here, we demonstrate that point mutations in the multifunctional meq gene acquired during evolution can significantly alter virulence. Defined mutations found in highly virulent strains also allowed the virus to overcome innate cellular responses and vaccinal protection. Concomitantly, the adaptations in meq enhanced virus shedding into the environment, likely providing a selective advantage for the virus. Our study provides the first experimental evidence that few point mutations in a single herpesviral gene result in drastically increased virulence, enhanced shedding, and escape from vaccinal protection.

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Section: Plos Pathogenssupporting

confidence: 85%

Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance

et al. 2020

Self Cite

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“…Recently, with the aid of imaging mass spectrometry and proteomics, Pauker et al discovered that several novel proteins including IFN-γ-inducible protein 30 and a 70-kD heat shock protein were differentially expressed in tumor tissue compared to surrounding tissue and naive T cells, suggestive of potential MDV tumor markers. However, CD30 overexpression were not confirmed in the tumor tissue in this study [123].…”

Section: Cd4 + and Cd8 + T Cellscontrasting

confidence: 70%

Revisiting cellular immune response to oncogenic Marek’s disease virus: the rising of avian T-cell immunity

Yang

Dong

Hao

et al. 2020

Cell. Mol. Life Sci.

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Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. Although Marek's disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding of molecular and cellular immunity to MDV and its immunopathogenesis has significantly improved, but those findings about cellular immunity to MDV are largely out-of-date, hampering the development of more effective vaccines against MD. T-cell-mediated cellular immunity was thought to be of paramount importance against MDV. However, MDV also infects macrophages, B cells and T cells, leading to immunosuppression and T-cell lymphoma. Additionally, there is limited information about how uninfected immune cells respond to MDV infection or vaccination, specifically, the mechanisms by which T cells are activated and recognize MDV antigens and how the function and properties of activated T cells correlate with immune protection against MDV or MD tumor. The current review revisits the roles of each immune cell subset and its effector mechanisms in the host immune response to MDV infection or vaccination from the point of view of comparative immunology. We particularly emphasize areas of research requiring further investigation and provide useful information for rational design and development of novel MDV vaccines.

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“…After cell lysis, 20 µg aliquots were digested using the FASP protocol as described [43]. Samples were differentially labeled by dimethylation [44] using unlabeled and 13 C-labeled formaldehyde, respectively, and subjected to nano-LC MALDI-TOF/TOF mass spectrometry as described previously [45]. Briefly, peptides were separated by nano reversed-phase liquid chromatography (EASY-nLC II, Bruker; Bremen, Germany), spotted to a MALDI target (Proteineer fcII, Bruker), and analyzed with an UltrafleXtreme MALDI-TOF/TOF mass spectrometer (Bruker) as described previously [46].…”

Section: Methodsmentioning

confidence: 99%

The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

Bertzbach

Pfaff

Pauker

et al. 2019

Viruses

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Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and poses a serious threat to poultry health. In infected animals, MDV efficiently replicates in B cells in various lymphoid organs. Despite many years of research, the viral transcriptome in primary target cells of MDV remained unknown. In this study, we uncovered the transcriptional landscape of the very virulent RB1B strain and the attenuated CVI988/Rispens vaccine strain in primary chicken B cells using high-throughput RNA-sequencing. Our data confirmed the expression of known genes, but also identified a novel spliced MDV gene in the unique short region of the genome. Furthermore, de novo transcriptome assembly revealed extensive splicing of viral genes resulting in coding and non-coding RNA transcripts. A novel splicing isoform of MDV UL15 could also be confirmed by mass spectrometry and RT-PCR. In addition, we could demonstrate that the associated transcriptional motifs are highly conserved and closely resembled those of the host transcriptional machinery. Taken together, our data allow a comprehensive re-annotation of the MDV genome with novel genes and splice variants that could be targeted in further research on MDV replication and tumorigenesis.

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Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors

Cited by 11 publications

References 70 publications

Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance

Distinct polymorphisms in a single herpesvirus gene are capable of enhancing virulence and mediating vaccinal resistance

Revisiting cellular immune response to oncogenic Marek’s disease virus: the rising of avian T-cell immunity

The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

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