Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity.

Diagnosis of Dengue Virus Infections Imported to Hungary and Phylogenetic Analysis of Virus Isolates.

Background: Dengue virus is one of the most important arbovirus infections of public health concern. Between 2017 and June 2022, 75 imported dengue infections were confirmed by laboratory diagnostic methods in Hungary. Our study aimed to isolate the imported Dengue strains and characterize them by whole-genome sequencing.

[Imported tropical arbovirus infections in Hungary between 2016 and 2020].

Unlabelled: Összefoglaló. Bevezetés: A Dengue-, Zika- és Chikungunya-vírus-fertőzések a trópusokról importált leggyakoribb arbovírusfertőzések. Földrajzi elterjedésük átfedő, közös vektoraik és hasonló tüneteik miatt szerológiai és molekuláris módszerek együttes alkalmazásán alapuló mikrobiológiai vizsgálatokkal különíthetők el megbízhatóan.

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.

Extraordinary increase in West Nile virus cases and first confirmed human Usutu virus infection in Hungary, 2018.

BackgroundDuring the 2018 WNV transmission season, similarly to other endemic areas in Europe, a large number of human West Nile virus (WNV) infections were reported in Hungary.AimsWe summarise the epidemiological and laboratory findings of the 2018 transmission season and expand experiences in flavivirus differential diagnostics.MethodsEvery patient with clinical suspicion of acute WNV infection was in parallel tested for WNV, tick-borne encephalitis virus and Usutu virus (USUV) by serological methods.

Terminal Repeat Analysis of EBV Genomes.

Epstein-Barr virus (EBV) was the first human virus associated directly with human malignancies. During EBV infection of various host cells the double-stranded linear EBV DNA carried by the virions undergoes circularization. Since there are variable numbers of terminal repetitions (TRs) at the ends of the linear EBV genome, the resulting circular episomes enclose a variable number of TRs.

The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia.

The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of progression to prolymphocytoid transformation (PLL). This pair of lines is unique in several respects. Their common clonal origin was proven by the rearrangement of the immunoglobulin genes.

The role of DNA hypomethylation, histone acetylation and in vivo protein-DNA binding in Epstein-Barr virus-induced CD23 upregulation.

We analyzed epigenetic marks at the CD23 regulatory regions in well characterized Epstein-Barr virus (EBV)-carrying cell lines covering the major latency types. Bisulfite sequencing showed that DNA methylation is not a major regulator of EBV-induced CD23 transcription, although a wide hypomethylated DNA sequence in the regulatory regions is always present in the cell lines with high CD23 expression. Acetylated histone H3 levels at the CD23b promoter showed strong correlation with CD23b expression, while a weaker correlation could be observed at the CD23a core promoter.

The 5' regulatory sequences of active miR-146a promoters are hypomethylated and associated with euchromatic histone modification marks in B lymphoid cells.

Although the microRNA miR-146a is an important regulator of immunological processes and contributes to the pathogenesis of certain B cell lymphoma types, in B cells the epigenetic regulation of miR-146a expresion has not been studied yet. To elucidate the mechanisms controlling miR-146a expression in B lymphoid cells we analysed epigenetic marks, including CpG methylation and histone modifications, at the miR-146a promoter in well characterized Epstein-Barr virus (EBV) positive and EBV negative B cell lines. In addition, EBV positive epithelial cell lines were also studied as controls.

Molecular epidemiological analysis of env and pol sequences in newly diagnosed HIV type 1-infected, untreated patients in Hungary.

The aim of our study was to monitor the diversity of HIV-1 strains circulating in Hungary and investigate the prevalence of resistance-associated mutations to reverse transcriptase (RT) and protease (PR) inhibitors in newly diagnosed, drug-naive patients. A total of 30 HIV-1-infected patients without prior antiretroviral treatment diagnosed during the period 2008-2010 were included into this study. Viral subtypes and the presence of RT, PR resistance-associated mutations were established by sequencing.

Epigenetic regulation of latent Epstein-Barr virus promoters.

Epigenotypes are modified cellular or viral genotypes that differ in transcriptional activity in spite of having an identical or nearly identical DNA sequence. Restricted expression of latent, episomal Epstein-Barr virus (EBV) genomes is a consequence of a series of epigenetic modifications. In tight latency, there is no virus production (lytic viral replication, associated with the expression of all viral genes), and only a limited set of viral promoters is activated in a host-cell-dependent manner.

Binding of CCCTC-binding factor in vivo to the region located between Rep* and the C promoter of Epstein-Barr virus is unaffected by CpG methylation and does not correlate with Cp activity.

In this study, the binding of the insulator protein CCCTC-binding factor (CTCF) to the region located between Rep* and the C promoter (Cp) of Epstein-Barr virus (EBV) was analysed using chromatin immunoprecipitation and in vivo footprinting. CTCF binding was found to be independent of Cp usage in cell lines corresponding to the major EBV latency types. Bisulfite sequencing and an electrophoretic mobility-shift assay (using methylated and unmethylated probes) revealed that CTCF binding was insufficient to induce local CpG demethylation in certain cell lines and was unaffected by CpG methylation in the region between Rep* and Cp.

The importance of epigenetic alterations in the development of epstein-barr virus-related lymphomas.

Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with a series of malignant tumors. These include lymphomas (Burkitt's lymphoma, Hodgkin's disease, T/NK-cell lymphoma, post-transplant lymphoproliferative disease, AIDS-associated lymphoma, X-linked lymphoproliferative syndrome), carcinomas (nasopharyngeal carcinoma, gastric carcinoma, carcinomas of major salivary glands, thymic carcinoma, mammary carcinoma) and a sarcoma (leiomyosarcoma). The latent EBV genomes persist in the tumor cells as circular episomes, co-replicating with the cellular DNA once per cell cycle.

Latency type-specific distribution of epigenetic marks at the alternative promoters Cp and Qp of Epstein-Barr virus.

Transcripts for the Epstein-Barr virus (EBV)-encoded nuclear antigens are initiated at the alternative promoters Wp, Cp and Qp. Although the host cell-dependent activity of Cp is regulated by DNA methylation, Qp is unmethylated independently of its activity. Because histone modifications affect the chromatin structure, we compared the levels of diacetylated histone H3, tetraacetylated histone H4 and histone H3 dimethylated on lysine 4 (H3K4me2) at Cp and Qp, in well characterized cell lines representing the major EBV latency types.

Lineage-specific silencing of human IL-10 gene expression by promoter methylation in cervical cancer cells.

Epigenetic analysis was performed to demonstrate that the normal and neoplastic epithelial cells do not serve as the source of the locally elevated IL-10 production during cervical carcinogenesis. Bisulfite sequencing was used to correlate promoter CpG methylation with the transcription of the gene. Lack of IL-10 transcription in HeLa, SiHa, Caski, HT-3, C33-A, HaCaT cell lines and in primary human keratinocytes correlated consistently with the methylated state of the proximal CpG residues, particularly with the two most proximal CpGs at positions -185 and -110.

CpG-methylation silences the activity of the RNA polymerase III transcribed EBER-1 promoter of Epstein-Barr virus.

CpG-methylation blocks the activity of RNA polymerase II transcribed promoters in most cases. In contrast, the role of DNA methylation in the regulation of RNA polymerase III transcribed promoters is less clarified. There are two untranslated viral RNAs (EBER-1 and EBER-2) in most malignant cells carrying latent Epstein-Barr virus (EBV) genomes.

Acetylated histone H3 and H4 mark the upregulated LMP2A promoter of Epstein-Barr virus in lymphoid cells.

We analyzed the levels of acetylated histones and histone H3 dimethylated on lysine 4 (H3K4me2) at the LMP2A promoter (LMP2Ap) of Epstein-Barr virus in well-characterized type I and type III lymphoid cell line pairs and additionally in the nasopharyngeal carcinoma cell line C666-1 by using chromatin immunoprecipitation. We found that enhanced levels of acetylated histones marked the upregulated LMP2Ap in lymphoid cells. In contrast, in C666-1 cells, the highly DNA-methylated, inactive LMP2Ap was also enriched in acetylated histones and H3K4me2.

High-resolution analysis of CpG methylation and in vivo protein-DNA interactions at the alternative Epstein-Barr virus latency promoters Qp and Cp in the nasopharyngeal carcinoma cell line C666-1.

Transcripts for the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNAs) are initiated at alternative promoters (Wp, Cp, for EBNA 1-6 transcripts and Qp, for EBNA 1 transcripts only) located in the BamHI W, C or Q fragment of the viral genome. To understand the host-cell dependent expression of EBNAs in EBV-associated tumors (lymphomas and carcinomas) and in vitro transformed cell lines, it is necessary to analyse the regulatory mechanisms governing the activity of the alternative promoters of EBNA transcripts. Such studies focused mainly on lymphoid cell lines carrying latent EBV genomes, due to the lack of EBV-associated carcinoma cell lines maintaining latent EBV genomes during cultivation in tissue culture.

A 30 kb region of the Epstein-Barr virus genome is colinear with the rearranged human immunoglobulin gene loci: implications for a "ping-pong evolution" model for persisting viruses and their hosts. A review.

The left part of the Epstein-Barr virus (EBV) genome exhibits a strong colinearity of structural and functional elements with the immunoglobulin (Ig) gene loci which is only partially reflected in nucleotide sequence homologies. We propose that this colinearity may be the result of an inter-dependent co-evolution of the immunoglobulin loci together with EBV. Our observation could help elucidating the mechanisms of somatic hypermutation, explaining the ability of EBV to accidentally cause tumors, and shedding more light on the general mechanisms of viral and organismal evolution.

EBV-associated neoplasms: alternative pathogenetic pathways.

We propose that there are two main classes of Epstein-Barr virus (EBV) associated lymphomas: primarily malignant Burkitt's Lymphoma (BL) and Hodgkin's Disease (HD), on one hand, and primarily benign lymphoproliferations, e.g., post-transplant lymphoproliferative disease (PTLD) on the other hand.

The in vivo binding site for oncoprotein c-Myc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis.

Background: Epstein-Barr virus (EBV) was isolated in the 1960s from the African childhood tumor, Burkitt's Lymphoma (BL), characterized by the translocation of the c-myc gene into one of the immunoglobulin loci. Due to the extreme discrepancy between the widespread dissemination of EBV infection and the overall rarity of EBV-related tumors, it remains an open question whether EBV is really a human tumor virus, and if so, what specific contribution EBV may have to tumorigenesis.

Material/methods: Protein binding at the EBER locus of EBV was analyzed by genomic footprinting electrophoretic mobility shift, reporter gene assay, and chromatin immunoprecipitation in a panel of six B-cell lines.