The oral microbiome of a family including Papillon-Lefèvre-syndrome patients and clinically healthy members.

AIMS: The oral microbiota composition of patients diagnosed with Papillon-Lefèvre-syndrome and treated for several years were compared to those existing in the oral cavity of the clinically healthy family members and a cohort of patients having various stages of chronic periodontitis. MATERIALS AND METHODS: A family with two sisters affected with severe periodontitis and with the typical skin symptoms of Papillon-Lefèvre-syndrome, and symptomless parents and third sibling were investigated. The Patients received periodontal treatment for several years and their oral microbiome was analysed by amplicon sequencing. Data were evaluated by microbial cluster analysis. RESULTS: The microbiome of the patients with Papillon-Lefèvre-syndrome was predominated with Aggregatibacter actinomycetemcomitans and associated oral periodontopathogens. Although the clinically healthy family members showed no oral disorder, their microbiome resembled that of subjects having mild periodontitis. CONCLUSIONS: Predominance of A. actinomycetemcomitans in the subgingival microbiome of patients with Papillon-Lefèvre-syndrome suggests that specific treatment strategies directed against this pathobiont may improve the oral health status of the affected individuals. TRIAL REGISTRATION: The study was conducted in accordance with the Declaration of Helsinki and the ethical permission has been issued by the Human Investigation Review Board of the University of Szeged, Albert Szent-Györgyi Clinical Centre (Permission No. 63/2017-SZTE). September 19, 2017.  https://u-szeged.hu/klinikaikutatas/rkeb-altal-jovahagyott/rkeb-2017 .

Human tumor viruses: induction of three-dimensional alterations in the host genome structure.

Certain viruses called tumor viruses or oncoviruses are capable to change the gene expression pattern of distinct human or animal cell types in tissue culture, resulting in uncontrolled proliferation as well as a change in the social behavior of the infected cells: the oncovirus-transformed, immortalized cells are capable to form malignant neoplasms in suitable animal models. At present, seven human viruses are categorized as causative agents of distinct human malignancies. The genomes of human tumor viruses, typically encode viral oncoproteins and non- translated viral RNAs that affect the gene expression pattern of their target cells or induce genetic and epigenetic alterations contributing to oncogenesis. Recently, the application of chromatin conformation capture technologies and three-dimensional (3D) molecular imaging techniques revealed how the gene products or genomes of certain human tumor viruses interact with and induce alterations in the 3D host genome structure. This Mini Review aims to cover selected aspects of these developments. The papers, discussed briefly, describe how insertion of a novel viral binding site for the 3D genome organizer cellular protein CCCTC-binding factor (CTCF) into the DNA of T cells infected by human T-cell lymphotropic virus type 1 (HTLV-1) may contribute to lymphomagenesis, as well as how integration of high risk human papillomavirus genome into the host cell DNA may facilitate cervical carcinogenesis. Recent results regarding the interactions of cellular genomes with the episomal, chromatinized DNA genomes of oncogenic human herpesvirus, Epstein-Barr virus (EBV) will also be summarized, similarly to available data regarding contacts formed by episomal or integrated hepatitis B virus (HBV) DNA with host chromatin. Finally, a putative mechanism of hepatitis C virus (HCV) induced chromatin alterations will be presented, which may solve the riddle, how a cytoplasmic RNA virus without a viral oncogene could induce malingnant transfrormation of hepatocytes.

Interaction of biomolecules with anatase, rutile and amorphous TiO2 surfaces: A molecular dynamics study.

The adhesion of biomolecules to dental and orthopedic implants is a fundamental step in the process of osseointegration. Short peptide motifs, such as RGD or KRSR, carried by extracellular matrix proteins or coated onto implant surfaces, accelerate cell adhesion and tissue formation. For this reason, understanding the binding mechanisms of adhesive peptides to oxidized surfaces of titanium implants is of paramount importance. We performed molecular dynamics simulations to compare the adhesion properties of 6 peptides, including the tripeptide RGD, its variants KGD and LGD, as well as the tetrapeptide KRSR, its variant LRSR and its truncated version RSR, on anatase, rutile, and amorphous titanium dioxide (TiO2) surfaces. The migration of these molecules from the water phase to the surface was simulated in an aqueous environment. Based on these simulations, we calculated the residence time of each peptide bound to the three different TiO2 structures. It was found that the presence of an N-terminal lysine or arginine amino acid residue resulted in more efficient surface binding. A pulling simulation was performed to detach the adhered molecules. The maximum pulling force and the binding energy were determined from the results of these simulations. The tri- and tetrapeptides had slightly greater adhesion affinity to the amorphous and anatase structure than to rutile in general, however specific surface and peptide binding characters could be detected. The binding energies obtained from our simulations allowed us to rank the adhesion strengths of the studied peptides.

Integrative profiling of Epstein-Barr virus transcriptome using a multiplatform approach.

BACKGROUND: Epstein-Barr virus (EBV) is an important human pathogenic gammaherpesvirus with carcinogenic potential. The EBV transcriptome has previously been analyzed using both Illumina-based short read-sequencing and Pacific Biosciences RS II-based long-read sequencing technologies. Since the various sequencing methods have distinct strengths and limitations, the use of multiplatform approaches have proven to be valuable. The aim of this study is to provide a more complete picture on the transcriptomic architecture of EBV. METHODS: In this work, we apply the Oxford Nanopore Technologies MinION (long-read sequencing) platform for the generation of novel transcriptomic data, and integrate these with other's data generated by another LRS approach, Pacific BioSciences RSII sequencing and Illumina CAGE-Seq and Poly(A)-Seq approaches. Both amplified and non-amplified cDNA sequencings were applied for the generation of sequencing reads, including both oligo-d(T) and random oligonucleotide-primed reverse transcription. EBV transcripts are identified and annotated using the LoRTIA software suite developed in our laboratory. RESULTS: This study detected novel genes embedded into longer host genes containing 5'-truncated in-frame open reading frames, which potentially encode N-terminally truncated proteins. We also detected a number of novel non-coding RNAs and transcript length isoforms encoded by the same genes but differing in their start and/or end sites. This study also reports the discovery of novel splice isoforms, many of which may represent altered coding potential, and of novel replication-origin-associated transcripts. Additionally, novel mono- and multigenic transcripts were identified. An intricate meshwork of transcriptional overlaps was revealed. CONCLUSIONS: An integrative approach applying multi-technique sequencing technologies is suitable for reliable identification of complex transcriptomes because each techniques has different advantages and limitations, and the they can be used for the validation of the results obtained by a particular approach.

Microbiomes in supragingival biofilms and saliva of adolescents with gingivitis and gingival health.

BACKGROUND: Important alterations exist in the microbiomes of supragingival biofilm and saliva samples from adolescent patients developing induced or spontaneous gingivitis relative to healthy controls. These and the relationships to dental health are not fully understood yet. SUBJECTS AND METHODS: Supragingival biofilm samples (n = 36) were collected from the teeth of 9 adolescents with gingivitis induced by orthodontic appliances, as well as dental plaques (n = 40) from 10 adolescents with spontaneous gingivitis, in addition to similar samples (n = 36) from 9 healthy controls. The bacterial metagenomes were analyzed by 16S rRNA gene amplicon sequencing. Salivary microbiomes of the same persons were characterized by shotgun metagenome sequencing. The data sets were examined using advanced bioinformatics workflows and two reference databases. RESULTS: The composition and diversity of bacterial communities did not differ extensively among the three study groups. Nevertheless, the relative abundances of the genera Fusobacterium, Akkermansia, Treponema, and Campylobacter were prominently higher in gingivitis patients versus controls. In contrast, the genera Lautropia, Kingella, Neisseria, Actinomyces, and Rothia were significantly more abundant in controls than in either of the two gingivitis groups. CONCLUSIONS: The abundance pattern of certain taxa rather than individual strains shows characteristic features of potential diagnostic value. Stringent bioinformatics treatment of the sequencing data is mandatory to avoid unintentional misinterpretations.

Interaction of KRSR Peptide with Titanium Dioxide Anatase (100) Surface: A Molecular Dynamics Simulation Study.

Due to its tensile strength and excellent biocompatibility, titanium (Ti) is commonly used as an implant material in medicine and dentistry. The success of dental implants depends on the formation of a contact between the oxidized surface of Ti implant and the surrounding bone tissue. The adsorption of proteins and peptides to the implant surface allows the bone-forming osteoblast cells to adhere to such modified surfaces. Recently, it has been observed that tetrapeptide KRSR (Lys-Arg-Ser-Arg) functionalization could promote osteoblast adhesion to implant surfaces. This may facilitate the establishment of an efficient bone-to implant contact and improve implant stability during the healing process. GROMACS, a molecular dynamics software package was used to perform a 200 ns simulation of adsorption of the KRSR peptide to the TiO2 (anatase) surface in an aqueous environment. The molecule conformations were mapped with Replica Exchange Molecular Dynamics (REMD) simulations to assess the possible peptide conformations on the anatase surface, and the umbrella sampling method was used to calculate the binding energy of the most common conformation. The simulations have shown that the KRSR peptide migrates and attaches to the surface in a stable position. The dominant amino acid residue interacting with the TiO2 surface was the N-terminal charged lysine (K) residue. REMD indicated that there is a distinct conformation that is taken by the KRSR peptide. In this conformation the surface interacts only with the lysine residue while the ser (S) and arg (R) residues interact with water molecules farther from the surface. The binding free energy of the most common conformation of KRSR peptide to the anatase (100) surface was ΔG = -8.817 kcal/mol. Our result suggests that the N-terminal lysine residue plays an important role in the adhesion of KRSR to the TiO2 surface and may influence the osseointegration of dental implants.

Bioactive coatings for dental implants: A review of alternative strategies to prevent peri-implantitis induced by anaerobic bacteria.

Members of oral bacterial communities form biofilms not only on tooth surfaces but also on the surface of dental implants that replace natural teeth. Prolonged interaction of host cells with biofilm-forming anaerobes frequently elicits peri-implantitis, a destructive inflammatory disease accompanied by alveolar bone loss leading to implant failure. Here we wish to overview how the deposition of bioactive peptides to dental implant surfaces could potentially inhibit bacterial colonization and the development of peri-implantisis. One preventive strategy is based on natural antimicrobial peptides (AMPs) immobilized on titanium surfaces. AMPs are capable to destroy both Gram positive and Gram negative bacteria directly. An alternative strategy aims at coating implant surfaces - especially the transmucosal part - with peptides facilitating the attachment of gingival epithelial cells and connective tissue cells. These cells produce AMPs and may form a soft tissue seal that prevents oral bacteria from accessing the apical part of the osseointegrated implant. Because a wide variety of titanium-bound peptides were studied in vitro, we wish to concentrate on bioactive peptides of human origin and some of their derivatives. Furthermore, special attention will be given to peptides effective under in vivo test conditions.

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Hungary.

Widespread introduction of HIV integrase inhibitors into clinical care may result in appearance of drug resistance mutations affecting treatment outcome. The aim of our study was to monitor the resistance patterns of integrase inhibitors beside protease and reverse transcriptase inhibitors in newly diagnosed therapy-naive HIV-positive patients in Hungary between 2017 and 2019.Genotype-based resistance testing of HIV integrase, protease and reverse transcriptase was performed by amplification and Sanger population sequencing from plasma samples. Drug resistance mutations were identified by the algorithm of Stanford HIV Drug Resistance Database.Potentially transmitted, non-polymorphic integrase major mutation was detected in 1 out of 249 samples, while accessory mutations were observed in further 31 patients (12.4%). The overall prevalence of transmitted drug resistance (TDR) mutations related to protease and reverse transcriptase inhibitors was 5.8% (10/173) between the end of 2017 and 2019. Nucleoside reverse transcriptase inhibitor associated resistance mutations were the most frequent indicators of TDR (6/173; 3.5%), followed by resistance mutations associated with protease (3/173; 1.7%) and non-nucleoside reverse transcriptase inhibitors (2/173, 1.2%).The first detection of integrase major mutation and the changing patterns of other resistance mutations in Hungarian untreated HIV-positive population indicate the necessity of continuous molecular surveillance of Hungarian HIV epidemic.

Toward Personalized Oral Diagnosis: Distinct Microbiome Clusters in Periodontitis Biofilms.

Periodontitis is caused by pathogenic subgingival microbial biofilm development and dysbiotic interactions between host and hosted microbes. A thorough characterization of the subgingival biofilms by deep amplicon sequencing of 121 individual periodontitis pockets of nine patients and whole metagenomic analysis of the saliva microbial community of the same subjects were carried out. Two biofilm sampling methods yielded similar microbial compositions. Taxonomic mapping of all biofilms revealed three distinct microbial clusters. Two clinical diagnostic parameters, probing pocket depth (PPD) and clinical attachment level (CAL), correlated with the cluster mapping. The dysbiotic microbiomes were less diverse than the apparently healthy ones of the same subjects. The most abundant periodontal pathogens were also present in the saliva, although in different representations. The single abundant species Tannerella forsythia was found in the diseased pockets in about 16-17-fold in excess relative to the clinically healthy sulcus, making it suitable as an indicator of periodontitis biofilms. The discrete microbial communities indicate strong selection by the host immune system and allow the design of targeted antibiotic treatment selective against the main periodontal pathogen(s) in the individual patients.

Anaerobic bacterial communities associated with oral carcinoma: Intratumoral, surface-biofilm and salivary microbiota.

It was estimated that more than 700 bacterial species inhabit the oral cavity of healthy humans. Anaerobes comprise a significant fraction of the oral bacteriome and play an important role in the formation of multi-species biofilms attached to various anatomical sites. Bacterial biofilms are also associated with pathologic laesions of the oral cavity, including oral squamous cell carcinoma (OSCC), and distinct oral taxa could also be detected within the tumors, i.e. in deep biopsy samples. These observations suggested that certain oral bacteria or oral bacterial communities may play a causative role in oral carcinogenesis, in addition to the well characterized risk factors of oral cancer. Alternatively, it was also proposed that a subset of oral bacteria may have a growth advantage in the unique microenvironment of OSCC. Recently, a series of studies analysed the OSCC-associated bacterial communities using metataxonomic, metagenomic and metatranscriptomic approaches. This review outlines the major differences between the community structure of microbiota in tumor biopsy, surface-biofilm and salivary or oral wash samples collected from OSCC patients, compared to corresponding samples from control persons. A special emphasis is given to the anaerobic bacteria Fusobacterium nucleatum and Fusobacterium periodonticum that were characterised repeatedly as "OSCC-associated" in independent studies. Predicted microbial functions and relevant in vivo experimental models of oral carcinogenesis will also be summarized.

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing.

OBJECTIVE: To investigate the role of cigarette smoking in disease-development through altering the composition of the oral microbial community. Periodontitis and oral cancer are highly prevalent in Hungary; therefore, the salivary microbiome of smoker and non-smoker Hungarian adults was characterized. METHODS: Shotgun metagenome sequencing of salivary DNA samples from 22 individuals (11 non-smokers and 11 current smokers) was performed using the Ion Torrent PGMTM platform. Quality-filtered reads were analysed by both alignment-based sequence similarity searches and genome-centric binning. RESULTS: Prevotella, Veillonella and Streptococcus were the predominant genera in the saliva of both groups. Although the overall composition and diversity of the microbiota were similar, Prevotella was significantly more abundant in salivary samples of current smokers compared to non-smokers. Members of the genus Prevotella were implicated in the development of inflammatory diseases and oral cancer. The abundance of the genus Megasphaera also increased in current smokers, whereas the genera Neisseria, Oribacterium, Capnocytophaga and Porphyromonas were significantly reduced. The data generated by read-based taxonomic classification and genome-centric binning mutually validated the two distinct metagenomic approaches. CONCLUSION: Smoking-associated dysbiosis of the salivary microbiome in current cigarette smokers, especially increased abundance of Prevotella and Megasphaera genera, may facilitate disease development.

Transmitted drug resistance in newly diagnosed and treatment-naïve HIV type 1-infected patients in Hungary.

OBJECTIVES: Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) may affect the success of first-line antiretroviral treatment. This study aimed to monitor the presence of HIV-1 strains carrying transmitted drug resistance-associated mutations (TDRMs) in newly diagnosed and treatment-naïve patients in Hungary. METHODS: This study included 168 HIV-infected individuals diagnosed between 2013-2017; most of them (93.5%) belonged to the homo/bisexual population. HIV-1 subtypes and TDRMs were determined by analysing the protease and reverse transcriptase coding regions of the pol gene by the Stanford HIV Drug Resistance Database. Transmission clusters among patients were identified using phylogenetic analysis. RESULTS: Although subtype B HIV-1 strains were predominant (87.5%), non-B subtypes including F, A, CRF01_AE, CRF02_AG, D and G were also recorded, especially in young adults. The overall prevalence of TDR was 10.7% (18 of 168; 95% CI: 6.9-16.3%). Subtype B HIV-1 strains carried most of the TDRMs (94.4%). Nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were the most prevalent indicators of TDR (16 of 168; 9.5%; 95% CI: 5.9-14.9%), followed by mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2 of 168; 1.2%; 95% CI: 0.3-4.2%) and protease inhibitors (PIs) (1 of 168, 0.6%; 95% CI: 0.1-3.3%). Phylogenetic analysis revealed that most NRTI-associated resistance mutations were associated with a single monophyletic clade, suggesting early single-source introduction and ongoing spread of this drug-resistant HIV-1 strain. CONCLUSIONS: Onward transmission of drug-resistant subtype B HIV-1 strains accounted for the majority of TDRs observed among treatment-naïve HIV-infected individuals in Hungary.

Truncated oncoproteins of retroviruses and hepatitis B virus: A lesson in contrasts.

Members of the virus families Retroviridae and Hepadnaviridae use reverse transcriptase (RT) to synthesize a DNA copy of their genomic and pregenomic RNA, respectively, during the viral life cycle. A group of viruses belonging to Retroviridae ("acute transforming" retroviruses) as well as human hepatitis B virus (HBV), the prototype member of Hepadnaviridae (hepadnaviruses) are able to cause malignant neoplasms in infected hosts, due to the expression of pleiotropic "transforming proteins" encoded by the genomes of these reverse-transcribing tumor viruses. In this review we wish to compare the common and unique features of replication strategies characteristic of acute transforming retroviruses and HBV and summarize data related to the origin and evolution of their viral oncogenes either via transduction of cellular genes, or by accumulation of mutations in viral sequences that create a new open reading frame (overprinting). The exons of cellular genes (proto-onc genes or c-onc genes) incorporated into the genome of acute transforming retroviruses are regularly affected by deletions resulting in the expression of truncated viral oncoproteins which are frequently dysregulated compared to their cellular counterparts. These retroviral transforming proteins alter the behavior of their target cells (malignant transformation). HBx, a pleiotropic protein of HBV, regulates virus replication and contributes to hepatocarcinogenesis. In contrast to the v-onc genes of acute transforming retroviruses, the viral gene encoding the full-length, wild-type HBx (wtHBx) protein does not have a cellular counterpart. Mutations and deletions frequently affect, however, the HBV genome as well, resulting in the expression of truncated HBx proteins (trHBx) in liver cells. Truncated, especially C-terminal truncated variants of HBx (Ct-HBX proteins), may facilitate initiation and progression of liver carcinoma.

Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition.

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 µM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 µM, while it was a more potent integrase inhibitor already active at 2.15 µM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.

Chicken or the Egg: Microbial Alterations in Biopsy Samples of Patients with Oral Potentially Malignant Disorders.

Oral carcinogenesis often leads to the alteration of the microbiota at the site of the tumor, but data are scarce regarding the microbial communities of oral potentially malignant disorders (OPMDs). Punch biopsies were taken from healthy and non-healthy mucosa of OPMD patients to analyze the microbiome using metagenome sequencing. In healthy oral mucosa biopsies the bacterial phyla Firmicutes, Fusobacteria, Proteobacteria, Actinobacteria and Bacteroidetes were detected by Ion Torrent sequencing. The same phyla as well as the phyla Fibrobacteres and Spirochaetes were present in the OPMD biopsies. On the species level, there were 10 bacterial species unique to the healthy tissue and 35 species unique to the OPMD lesions whereas eight species were detected in both samples. We observed that the relative abundance of Streptococcus mitis decreased in the OPMD lesions compared to the uninvolved tissue. In contrast, the relative abundance of Fusobacterium nucleatum, implicated in carcinogenesis, was elevated in OPMD. We detected markedly increased bacterial diversity in the OPMD lesions compared to the healthy oral mucosa. The ratio of S. mitis and F. nucleatum are characteristically altered in the OPMD lesions compared to the healthy mucosa.

Prevalence and genotypes of human papillomavirus in saliva and tumor samples of head and neck cancer patients in Hungary.

In addition to traditional risk factors such as smoking, alcohol consumption and betel nut use, human papillomavirus (HPV) infection also plays a role in the development of head and neck squamous cell carcinomas (HNSCCs). Although among European countries the highest incidence and mortality rates of head and neck cancer types were recorded in Hungary, data regarding HPV prevalence in HNSCCs is scarce. We collected biopsy and saliva samples from patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) and tested them for the presence of HPV using the PCR consensus primer set MY09/11 and the GP5+/6+ primer pair. HPV genotypes were assessed by sequencing of the amplified PCR fragments. Oral mucosa and saliva samples from tumor- and OPMD-free individuals were also analysed. HPV was detected in 11 out of 60 HNSCC samples (18%). All of the HPV positive tumors carried HPV type 16. 5 out of the 57 saliva samples collected from HNSCC patients was HPV positive (8.8%); among them, in addition to HPV16, HPV13 was also detected. Tumors located to the oropharynx had the highest HPV positivity rate with 50% (7 out of 14), which was significantly higher than the HPV prevalence in oral mucosa samples collected from controls (0 out of 20; p > 0.001) or in OPMD biopsies (0 out of 21, p > 0.001). 2 out of 57 control saliva samples (3.5%, subtype HPV13 and 11) and 3 out of 39 saliva samples from OPMD patients (7.7%, subtype HPV18, 81 and 10) were HPV positive. Our data suggested that HPV16 infection may contribute, in concert with cigarette smoking, to the development of a subset of head and neck cancers in Hungary. HPV16 infection per se does not account, however, for the high HNSCC incidence rate recorded in this country.

Pathogenic mechanisms of intracellular bacteria.

PURPOSE OF REVIEW: We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. RECENT FINDINGS: DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression. Gene silencing by CpG methylation and histone deacetylation, mediated by cellular enzymes, also occurred in M. tuberculosis-infected macrophages. M. tuberculosis elicited cell type-specific epigenetic changes: it caused increased DNA methylation in macrophages, but induced demethylation, deposition of euchromatic histone marks and activation of immune-related genes in dendritic cells. A secreted transposase of Acinetobacter baumannii silenced a cellular gene, whereas Mycobacterium leprae altered the epigenotype, phenotype, and fate of infected Schwann cells. The 'keystone pathogen' oral bacterium Porphyromonas gingivalis induced local DNA methylation and increased the level of histone acetylation in host cells. These epigenetic changes at the biofilm-gingiva interface may contribute to the development of periodontitis. SUMMARY: Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells and play an important role in pathogenesis.

Current Trends and Alternative Scenarios in EBV Research.

Epstein-Barr virus (EBV) infection is associated with several distinct hematological and epithelial malignancies, e.g., Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. The association with several malignant tumors of local and worldwide distribution makes EBV one of the most important tumor viruses. Furthermore, because EBV can cause posttransplant lymphoproliferative disease, transplant medicine has to deal with EBV as a major pathogenic virus second only to cytomegalovirus. In this review, we summarize briefly the natural history of EBV infection and outline some of the recent advances in the pathogenesis of the major EBV-associated neoplasms. We present alternative scenarios and discuss them in the light of most recent experimental data. Emerging research areas including EBV-induced patho-epigenetic alterations in host cells and the putative role of exosome-mediated information transfer in disease development are also within the scope of this review. This book contains an in-depth description of a series of modern methodologies used in EBV research. In this introductory chapter, we thoroughly refer to the applications of these methods and demonstrate how they contributed to the understanding of EBV-host cell interactions. The data gathered using recent technological advancements in molecular biology and immunology as well as the application of sophisticated in vitro and in vivo experimental models certainly provided deep and novel insights into the pathogenetic mechanisms of EBV infection and EBV-associated tumorigenesis. Furthermore, the development of adoptive T cell immunotherapy has provided a novel approach to the therapy of viral disease in transplant medicine and hematology.

Detection and Phylogenetic Analysis of Torque Teno Virus in Salivary and Tumor Biopsy Samples from Head and Neck Carcinoma Patients.

OBJECTIVES: Because torque teno virus (TTV) has been implicated in tumorigenesis as a cocarcinogen, we studied TTV prevalence in saliva and biopsy samples from head and neck cancer (HNCC) patients, patients with premalignant lesions of oral cancer, and controls. We also wished to determine the TTV genotypes in HNCC patients. METHODS: A seminested polymerase chain reaction (PCR) amplifying the N22 region of the TTV genome, as well as direct sequencing of PCR fragments, was used. RESULTS: TTV prevalence was higher in HNCC patients (saliva: 27/71, 38%; tumor biopsy: 22/74, 30%) than in controls (saliva: 8/56, 14%; oral mucosa: 1/19, 5%). TTV prevalence was also high in patients with premalignant lesions of oral carcinoma (saliva: 9/18, 50%; biopsy: 5/21, 24%). By phylogenetic analysis, TTV belonging mostly to genotypes 1 and 2 was found in HNCC patients. In most of the cases, identical TTV strains were present in the biopsy and salivary sample of the same HNCC patient. In addition, the same TTV strain was detected in 2 laryngeal carcinoma biopsies obtained from 2 independent patients. CONCLUSIONS: Our data are compatible with the idea that TTV might act as a cocarcinogen in certain cases of HNCC. Alternatively, HNCC may facilitate either TTV replication or TTV entry into the saliva.