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Article ; Online: Hepatitis B Virus Integration into Transcriptionally Active Loci and HBV-Associated Hepatocellular Carcinoma

Maria Bousali / Timokratis Karamitros

Microorganisms, Vol 10, Iss 253, p

2022 Volume 253

Abstract: Hepatitis B Virus (HBV) DNA integrations into the human genome are considered major causative factors to HBV-associated hepatocellular carcinoma development. In the present study, we investigated whether HBV preferentially integrates parts of its genome ... ...

Abstract	Hepatitis B Virus (HBV) DNA integrations into the human genome are considered major causative factors to HBV-associated hepatocellular carcinoma development. In the present study, we investigated whether HBV preferentially integrates parts of its genome in specific genes and evaluated the contribution of the integrations in HCC development per gene. We applied dedicated in-house developed pipelines on all of the available HBV DNA integration data and performed a statistical analysis to identify genes that could be characterized as hotspots of integrations, along with the evaluation of their association with HBV-HCC. Our results suggest that 15 genes are recurrently affected by HBV integrations and they are significantly associated with HBV-HCC. Further studies that focus on HBV integrations disrupting these genes are mandatory in order to understand the role of HBV integrations in clonal advantage gain and oncogenesis promotion, as well as to determine whether inhibition of the HBV-disrupted genes can provide a therapy strategy for HBV-HCC.
Keywords	hepatitis B virus ; viral integration ; VIS ; pathogen–host interactions ; hepatocellular carcinoma ; HBV-HCC ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma

Maria Bousali / George Papatheodoridis / Dimitrios Paraskevis / Timokratis Karamitros

Microorganisms, Vol 9, Iss 1787, p

2021 Volume 1787

Abstract: Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It ... ...

Abstract	Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal–fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO’s commitment to eliminate HBV and viral hepatitis by 2030.
Keywords	hepatitis B virus ; HBV ; viral integration ; pathogen-host interactions ; insertional mutagenesis ; chronic hepatitis ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular and Clinical Prognostic Biomarkers of COVID-19 Severity and Persistence

Gethsimani Papadopoulou / Eleni Manoloudi / Nikolena Repousi / Lemonia Skoura / Tara Hurst / Timokratis Karamitros

Pathogens, Vol 11, Iss 311, p

2022 Volume 311

Abstract: The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses several challenges to clinicians, due to its unpredictable clinical course. The identification of laboratory biomarkers, specific ... ...

Abstract	The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses several challenges to clinicians, due to its unpredictable clinical course. The identification of laboratory biomarkers, specific cellular, and molecular mediators of immune response could contribute to the prognosis and management of COVID-19 patients. Of utmost importance is also the detection of differentially expressed genes, which can serve as transcriptomic signatures, providing information valuable to stratify patients into groups, based on the severity of the disease. The role of biomarkers such as IL-6, procalcitonin, neutrophil–lymphocyte ratio, white blood cell counts, etc. has already been highlighted in recently published studies; however, there is a notable amount of new evidence that has not been summarized yet, especially regarding transcriptomic signatures. Hence, in this review, we assess the latest cellular and molecular data and determine the significance of abnormalities in potential biomarkers for COVID-19 severity and persistence. Furthermore, we applied Gene Ontology (GO) enrichment analysis using the genes reported as differentially expressed in the literature in order to investigate which biological pathways are significantly enriched. The analysis revealed a number of processes, such as inflammatory response, and monocyte and neutrophil chemotaxis, which occur as part of the complex immune response to SARS-CoV-2.
Keywords	SARS-CoV-2 ; COVID-19 ; pandemic ; host immune response ; prognostic biomarker ; COVID-19 severity ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dual RNA-Seq Enables Full-Genome Assembly of Measles Virus and Characterization of Host–Pathogen Interactions

Timokratis Karamitros / Vasiliki Pogka / Gethsimani Papadopoulou / Ourania Tsitsilonis / Maria Evangelidou / Styliani Sympardi / Andreas Mentis

Microorganisms, Vol 9, Iss 1538, p

2021 Volume 1538

Abstract: Measles virus (MeV) has a negative-sense 15 kb long RNA genome, which is generally conserved. Recent advances in high-throughput sequencing (HTS) and Dual RNA-seq allow the analysis of viral RNA genomes and the discovery of viral infection biomarkers, ... ...

Abstract	Measles virus (MeV) has a negative-sense 15 kb long RNA genome, which is generally conserved. Recent advances in high-throughput sequencing (HTS) and Dual RNA-seq allow the analysis of viral RNA genomes and the discovery of viral infection biomarkers, via the simultaneous characterization of the host transcriptome. However, these host–pathogen interactions remain largely unexplored in MeV infections. We performed untargeted Dual RNA-seq in 6 pharyngeal and 6 peripheral blood mononuclear cell (PBMCs) specimens from patients with MeV infection, as confirmed via routine real-time PCR testing. Following optimised DNase treatment of total nucleic acids, we used the pharyngeal samples to build poly-A-enriched NGS libraries. We reconstructed the viral genomes using the pharyngeal datasets and we further conducted differential expression, gene-ontology and pathways enrichment analysis to compare both the pharyngeal and the peripheral blood transcriptomes of the MeV-infected patients vs. control groups of healthy individuals. We obtained 6 MeV genotype-B3 full-genome sequences. We minutely analyzed the transcriptome of the MeV-infected pharyngeal epithelium, detecting all known viral infection biomarkers, but also revealing a functional cluster of local antiviral and inflammatory immune responses, which differ substantially from those observed in the PBMCs transcriptome. The application of Dual RNA-seq technologies in MeV-infected patients can potentially provide valuable information on the virus genome structure and the cellular innate immune responses and drive the discovery of new targets for antiviral therapy.
Keywords	measles virus ; host response ; dual RNA-seq ; genome assembly ; transcriptome ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of Helicobacter pylori Infection and Its Major Virulence Factor CagA on DNA Damage Repair

Eleftherios Kontizas / Spyros Tastsoglou / Timokratis Karamitros / Yiannis Karayiannis / Panagoula Kollia / Artemis G. Hatzigeorgiou / Dionyssios N. Sgouras

Microorganisms, Vol 8, Iss 2007, p

2020 Volume 2007

Abstract: Helicobacter pylori infection induces a plethora of DNA damages. Gastric epithelial cells, in order to maintain genomic integrity, require an integrous DNA damage repair (DDR) machinery, which, however, is reported to be modulated by the infection. CagA ... ...

Abstract	Helicobacter pylori infection induces a plethora of DNA damages. Gastric epithelial cells, in order to maintain genomic integrity, require an integrous DNA damage repair (DDR) machinery, which, however, is reported to be modulated by the infection. CagA is a major H. pylori virulence factor, associated with increased risk for gastric carcinogenesis. Its pathogenic activity is partly regulated by phosphorylation on EPIYA motifs. Our aim was to identify effects of H. pylori infection and CagA on DDR, investigating the transcriptome of AGS cells, infected with wild-type, ΔCagA and EPIYA-phosphorylation-defective strains. Upon RNA-Seq-based transcriptomic analysis, we observed that a notable number of DDR genes were found deregulated during the infection, potentially resulting to base excision repair and mismatch repair compromise and an intricate deregulation of nucleotide excision repair, homologous recombination and non-homologous end-joining. Transcriptome observations were further investigated on the protein expression level, utilizing infections of AGS and GES-1 cells. We observed that CagA contributed to the downregulation of Nth Like DNA Glycosylase 1 (NTHL1), MutY DNA Glycosylase (MUTYH), Flap Structure-Specific Endonuclease 1 (FEN1), RAD51 Recombinase, DNA Polymerase Delta Catalytic Subunit (POLD1), and DNA Ligase 1 (LIG1) and, contrary to transcriptome results, Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) upregulation. Our study accentuates the role of CagA as a significant contributor of H. pylori infection-mediated DDR modulation, potentially disrupting the balance between DNA damage and repair, thus favoring genomic instability and carcinogenesis.
Keywords	Helicobacter pylori ; CagA ; DNA damage repair ; gastric carcinogenesis ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: De Novo Assembly of Human Herpes Virus Type 1 (HHV-1) Genome, Mining of Non-Canonical Structures and Detection of Novel Drug-Resistance Mutations Using Short- and Long-Read Next Generation Sequencing Technologies.

Timokratis Karamitros / Ian Harrison / Renata Piorkowska / Aris Katzourakis / Gkikas Magiorkinis / Jean Lutamyo Mbisa

PLoS ONE, Vol 11, Iss 6, p e

2016 Volume 0157600

Abstract: Human herpesvirus type 1 (HHV-1) has a large double-stranded DNA genome of approximately 152 kbp that is structurally complex and GC-rich. This makes the assembly of HHV-1 whole genomes from short-read sequencing data technically challenging. To improve ... ...

Abstract	Human herpesvirus type 1 (HHV-1) has a large double-stranded DNA genome of approximately 152 kbp that is structurally complex and GC-rich. This makes the assembly of HHV-1 whole genomes from short-read sequencing data technically challenging. To improve the assembly of HHV-1 genomes we have employed a hybrid genome assembly protocol using data from two sequencing technologies: the short-read Roche 454 and the long-read Oxford Nanopore MinION sequencers. We sequenced 18 HHV-1 cell culture-isolated clinical specimens collected from immunocompromised patients undergoing antiviral therapy. The susceptibility of the samples to several antivirals was determined by plaque reduction assay. Hybrid genome assembly resulted in a decrease in the number of contigs in 6 out of 7 samples and an increase in N(G)50 and N(G)75 of all 7 samples sequenced by both technologies. The approach also enhanced the detection of non-canonical contigs including a rearrangement between the unique (UL) and repeat (T/IRL) sequence regions of one sample that was not detectable by assembly of 454 reads alone. We detected several known and novel resistance-associated mutations in UL23 and UL30 genes. Genome-wide genetic variability ranged from <1% to 53% of amino acids in each gene exhibiting at least one substitution within the pool of samples. The UL23 gene had one of the highest genetic variabilities at 35.2% in keeping with its role in development of drug resistance. The assembly of accurate, full-length HHV-1 genomes will be useful in determining genetic determinants of drug resistance, virulence, pathogenesis and viral evolution. The numerous, complex repeat regions of the HHV-1 genome currently remain a barrier towards this goal.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach

Evangelia-Georgia Kostaki / Timokratis Karamitros / Garyfallia Stefanou / Ioannis Mamais / Konstantinos Angelis / Angelos Hatzakis / Anna Kramvis / Dimitrios Paraskevis

eLife, Vol

2018 Volume 7

Abstract: Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and ... ...

Abstract	Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by the reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.
Keywords	hepatitis B virus ; phylogeny ; phylogeography ; global dispersal ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 Molecular Transmission Clusters and Containment Measures in Ten European Regions During the First Pandemic Wave

Maria Bousali / Aristea Dimadi / Evangelia-Georgia Kostaki / Sotirios Tsiodras / Georgios K. Nikolopoulos / Dionyssios N. Sgouras / Gkikas Magiorkinis / George Papatheodoridis / Vasiliki Pogka / Giota Lourida / Aikaterini Argyraki / Emmanouil Angelakis / George Sourvinos / Apostolos Beloukas / Dimitrios Paraskevis / Timokratis Karamitros

Life, Vol 11, Iss 219, p

2021 Volume 219

Abstract: Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome ...

Abstract	Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome SARS-CoV-2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation. Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super-spreading event found in Uusimaa-FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50–100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0–19 y.o. decreased only in those regions where schools’ closure was combined with a lockdown. Conclusions: The spatiotemporal profiling of the SARS-CoV-2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing.
Keywords	SARS-CoV-2 ; COVID-19 ; pandemic ; transmission ; clusters ; phylodynamics ; Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Harry A. Thorpe / Elise Tourrette / Koji Yahara / Filipa F. Vale / Siqi Liu / Mónica Oleastro / Teresa Alarcon / Tsachi-Tsadok Perets / Saeid Latifi-Navid / Yoshio Yamaoka / Beatriz Martinez-Gonzalez / Ioannis Karayiannis / Timokratis Karamitros / Dionyssios N. Sgouras / Wael Elamin / Ben Pascoe / Samuel K. Sheppard / Jukka Ronkainen / Pertti Aro /

Lars Engstrand / Lars Agreus / Sebastian Suerbaum / Kaisa Thorell / Daniel Falush

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: Helicobacter pylori is a major human pathogen whose population structure is similar to that of its host. Here, the authors show that H. pylori has repeatedly spread out of Africa recently, replacing deleterious variants that accumulated during the ... ...

Abstract	Helicobacter pylori is a major human pathogen whose population structure is similar to that of its host. Here, the authors show that H. pylori has repeatedly spread out of Africa recently, replacing deleterious variants that accumulated during the original out of Africa migrations more than 50,000 years ago.
Keywords	Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of smoking cessation, coffee and bread consumption on the intestinal microbial composition among Saudis

Steve Harakeh / Emmanouil Angelakis / Timokratis Karamitros / Dipankar Bachar / Suhad Bahijri / Ghada Ajabnoor / Sulaiman M Alfadul / Suha A Farraj / Turki Al Amri / Ahmed Al-Hejin / Abdalla Ahmed / Ahmed A Mirza / Raoult Didier / Esam I Azhar

PLoS ONE, Vol 15, Iss 4, p e

A cross-sectional study.

2020 Volume 0230895

Abstract: The gut microbiota is often affected by the dietary and lifestyle habits of the host, resulting in a better efficacy that favors energy harvesting from the consumed food. Our objective was to characterize the composition of gut microbiota in adult Saudis ...

Abstract	The gut microbiota is often affected by the dietary and lifestyle habits of the host, resulting in a better efficacy that favors energy harvesting from the consumed food. Our objective was to characterize the composition of gut microbiota in adult Saudis and investigate possible association with lifestyle and dietary practices. Feces from 104 Saudi volunteers (48% males) were tested for microbiota by sequencing the V3-V4 region of bacterial 16S ribosomal RNA (rRNA). For all participants, data were collected related to their lifestyle habits and dietary practices. The relative abundance (RA) of Fusobacteria was significantly higher in normal weight Saudis (P = 0.005, false discovery rate-FDR = 0.014). Individuals who consumed more coffee presented marginally significant more RA of Fusobacteria (P = 0.02, FDR = 0.20) in their gut microbiota compared to those reporting low or no coffee intake, but the RA of Fusobacteria was significantly higher in smokers compared to non-smokers (P = 0.009, FDR = 0.027). The RA of Fusobacteria was also significantly higher in those reporting daily consumption of bread (P = 0.005, FDR = 0.015). At the species level, the gut microbiota of people who consumed coffee was dominated by Bacteroides thetaiotaomicron followed by Phascolarctobacterium faecium and Eubacterium rectale. Similarly, the gut microbiota of smokers was also enriched by B. thetaiotaomicron and Lactobacillus amylovorus. Smoking cessation, bread and coffee consumption induce changes in the intestinal microbial composition of Saudis. This indicates the significance of diet and lifestyle practices in the determination of the composition of the gut microbiota, which could possibly lead later to changes in metabolic profile and weight.
Keywords	Medicine ; R ; Science ; Q
Subject code	910
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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