Janos Minarovits – författare

This volume provides an overview of the latency strategies developed during the estimated 200,000 year-long coevolution of Alpha-, Beta- and Gammaherpesvirinae and their host species. While the main emphasis is on herpesviruses infecting humans, relevant cases if herpesviruses infecting animals are covered as well. Special emphasis is given to results on molecular mechanisms regulating latent promoters of herpesvirus genomes and signals and molecular pathways resulting in reactivation of latent viral genomes.

This volume provides an overview of the latency strategies developed during the estimated 200,000 year-long coevolution of Alpha-, Beta- and Gammaherpesvirinae and their host species. While the main emphasis is on herpesviruses infecting humans, relevant cases if herpesviruses infecting animals are covered as well. Special emphasis is given to results on molecular mechanisms regulating latent promoters of herpesvirus genomes and signals and molecular pathways resulting in reactivation of latent viral genomes.

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences.Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to “remember” their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of humandiseases.

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences.Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to “remember” their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of humandiseases.

This volume explores data from the applications of molecular biological methods and the applications of recent immunological and cytogenetic methods in Epstein-Barr Virus (EBV) that will offer readers possible new solutions to the unresolved problems in the EBV field. Chapters in this book cover topics such as: viral life cycle, latency, EBV-associated diseases and EBV diagnostics; in vitro methods including organotypic cultures for the analysis of EBV-epithelial cell interactions; identification of the interacting viral and cellular proteins using affinity purification-mass spectrometry methods; 3D telomere FISH; transcription analysis using high-throughput RNA sequencing, qPCR and nuclear run-on assay; analysis of viral and cellular microRNAs; isolation and characterization of exosomes and the assessment of their function; characterization of the viral genome by terminal repeat analysis and sequencing; the use of chromatin immunoprecipitation coupled sequencing (ChIP-Seq) for theanalysis of Zta-DNA interactions; epigenetic analysis by bisulfite sequencing and ChIP; novel in vivo models for the study of EBV infection; and how immunological, virological, tissue culture and molecular methods can be combined to yield Good Manufacturing Practice-compliant EBV-specific T cells for the immunotherapy of EBV-associated post-transplant lymphoproliferative diseases (PTLD). Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.Cutting-edge and comprehensive, Epstein Barr-Virus: Methods and Protocols is a valuable resource for anyone who is interested in this fascinating and evolving field.

This volume explores data from the applications of molecular biological methods and the applications of recent immunological and cytogenetic methods in Epstein-Barr Virus (EBV) that will offer readers possible new solutions to the unresolved problems in the EBV field.

Epigenetic modification of cellular genomes is a fascinating means of regulating tissue- and cell type-specific gene expression in all developmental stages of the life of an organism. Carefully orchestrated processes, such as DNA methylation and a plenitude of specific histone modifications secure the faithful transmission of gene expression patterns to progeny cells. Upon chronic infection, the epigenetic cellular balance can become disrupted and, in the long run, through the epigenetic reprogramming of host cell genomes, contribute to the malignant conversion of formerly healthy cells, in many cases preceded by the establishment of an epigenetic field of cancerization. The present volume undertakes to highlight the interactions of infectious pathogens and their effector molecules with the epigenetic regulatory machinery of the cell. Clearly, the recent take-off of epigenetics research did not leave Research on Infectious Diseases and Infection-Associated Cancer untouched. This resulted in a great many of clinically relevant data on understanding the molecular mechanisms of chronic infectious disease. Infectious pathogen- and disease-specific epigenetic alterations are already being used for the early detection of malignant disease and for the prediction of chemotherapy resistance or response to treatment.