Epigenetics and animal virus infections.

Abstract

Epigenetics, modifications of the genome, heritable during celldivision, that do not involve changes in DNA sequences includeseveral mechanisms mainly: histone modifications, DNA methy-lation and related modifications, non-coding RNAs (ncRNAs)and others that regulate gene expression.The past two decades has seen an explosion of interestfor revealing mechanisms that control epigenetic modifications,mainly based on the influence they have on chromatin struc-tureandtheirimpactinbiologicalprocessessuchasprogrammedDNA rearrangements, imprinting, germ line silencing, devel-opmentally cued stem cell division, and overall chromosomalstability and identity. It has also become obvious that epigenet-ics changes are fundamental in the interplay between viruses andtheir host cells. Generally speaking, when retroviruses and DNAviruses integrate their genomes into the host genome, they canstay latent by silencing their genes or can be productive by acti-vatingthem,andviralgeneexpressioncanberegulatedjustlikeasthe host. In fact, viral DNA uses host transcription factors as wellas epigenetic regulators, in such a way that the effect of viral epi-geneticcontrolofitsowngeneexpressionalsoextendstoregulatehost gene expression. At the same time cells use similar mech-anisms, transcription factors and epigenetic modifications, inorder to try to eliminate viral infections. In summary, epigeneticmechanisms are involved in most of the virus-cell interactions.The goal of this special issue is to bring together key exper-imental and theoretical research linking state-of-the-art knowl-edge of epigenetic mechanisms involved in regulating virus-cellinteractions.This e-book is a compilation of 12 articles. Two of them aremethodological, one on the use of new technologies devoted toidentify methylated CpG sites on virus genomes and the other ongenome-wide mapping of DNase I hypersenitive sites associatedwith gene expression. Three articles describe original researchinvolvingSV40minichromosomes,DNAmethylationfluctuationand the Toll-like receptor pathways. Seven are review articles,including two mini-reviews on Epigenetic Mechanisms associ-ated to Hepatitis B Virus (HBV) and fundamental topics as DNAmethylation,histonemodificationsandviralstrategiesagainstthehost immune system in Epstein B Virus; cell differentiation ofthe immune system as a tool for epigenetic studies; epigeneticmechanisms associated to virotherapy, and finally on the recog-nition of DNA viruses and cell damage by histones.ThearticlefromSunetal.(2014),isamethodologyarticledes-ignatingtherelativeadvantagesoftheNGStechnologycomparedto pyrosequencing for studying viral DNA methylation. The ana-lytical procedure they used provided further information relatedto HPV methylation on a single cell basis, showing that there areHPV 16 genomic sequences in cells which are mostly methylatedwhile in others they are unmethylated (methylation mosaic).Replication of SV40minichromosomes can serve as an epige-netic switch in which newly replicated chromatin can be epige-neticallymodifiedinresponsetospecificsignalssuchasT-antigenbindingtositeI.Thisepigeneticswitchseemstoensurethatnewlyreplicated minichromosomes do not activate early transcriptionat late times in infection. In addition, this epigenetic switch maycontrol the relative pool sizes of transcribing, replicating, andencapsidating SV40minichromosomes. In an original researcharticle, Kallestad et al. (2013), shows that in cells containingSV40minichromosomes, histone modifications associated withchromatin repression can differ significantly depending uponwhether the chromatin is being repressed, undergoes transcrip-tion or replication.The review from Russ et al. (2013), describes advantages ofstudying the immune system for epigenetic regulation of celldifferentiation, in particular how T cell identity or plasticity iscontrolled. The authors focus some of the key findings and gen-eral themes emerging from the studies of T cell differentiation,as well as the utility of the immune system as a tool for studyingdifferentiation and development.Histonesareessentialcomponentsofchromatinstructure,andhistone modification plays an important role in various cellularfunctions including transcription, gene silencing, and immunity.Inaddition,histonesalsoplaydistinctrolesinextrachromosomalsettings. Kobiyama et al. (2013), in their review describe the roleof histone H2B as a sensor for dsDNA aberrantly present withinthe cells. According to the results included, extracellular andextrachromosomal histones alert cells to dangerous situations,such as infection, apoptosis, DNA breaks, and cell injury.Hepatitis B virus (HBV) infection is a global health problemcausing a wide spectrum of liver diseases, including acute andchronicinfection.AcuteHBVinfectionseitherresolveorprogressto chronic hepatitis, cirrhosis, and hepatocellular carcinoma.Because for most patients, available therapies do not lead tothe termination of HBV infection, improving our understanding