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Article ; Online: Improved hepatitis delta virus genome characterization by single molecule full-length genome sequencing combined with VIRiONT pipeline.

Charre, Caroline / Regue, Hadrien / Dény, Paul / Josset, Laurence / Chemin, Isabelle / Zoulim, Fabien / Scholtes, Caroline

Journal of medical virology

2023 Volume 95, Issue 3, Page(s) e28634

Abstract: Hepatitis B virus (HBV) and hepatitis D virus (HDV) coinfection confers a greater risk for accelerated liver disease progression. Full-length characterization of HDV genome is necessary to understand pathogenesis and treatment response. However, owing to ...

Abstract	Hepatitis B virus (HBV) and hepatitis D virus (HDV) coinfection confers a greater risk for accelerated liver disease progression. Full-length characterization of HDV genome is necessary to understand pathogenesis and treatment response. However, owing to its high variability and tight structure, sequencing approaches remain challenging. Herein, we present a workflow to amplify, sequence, and analyze the whole HDV genome in a single fragment. Sequencing was based on the Oxford Nanopore Technologies long-read sequencing followed by a turnkey analysis pipeline (VIRiONT, VIRal in-house ONT sequencing analysis pipeline) that we developed and make available online for free. For the first time, HDV genome was successfully amplified and full-length sequenced in a single fragment, allowing accurate subtyping from 30 clinical samples. High variability of edition, a crucial step in viral life cycle, was found among samples (from 0% to 59%). Additionally, a new subtype of HDV genotype 1 was identified. We provide a complete workflow for assessment of HDV genome at full-length quasispecies resolution overcoming genome assembly issues and helping to identify modifications throughout the whole genome. This will help a better understanding of the impact of genotype/subtype, viral dynamics, and structural variants on HDV pathogenesis and treatment response.
MeSH term(s)	Humans ; Hepatitis Delta Virus/genetics ; Hepatitis D ; Hepatitis B ; Hepatitis B virus/genetics ; Genotype ; Coinfection
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28634
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Article ; Online: ICTV Virus Taxonomy Profile:

Kuhn, Jens H / Babaian, Artem / Bergner, Laura M / Dény, Paul / Glebe, Dieter / Horie, Masayuki / Koonin, Eugene V / Krupovic, Mart / Paraskevopoulou, Sofia / de la Peña, Marcos / Smura, Teemu / Hepojoki, Jussi

The Journal of general virology

2024 Volume 105, Issue 2

Abstract: ... ...

Abstract	Kolmioviridae
MeSH term(s)	Animals ; Humans ; Helper Viruses ; Viroids ; Biological Evolution ; Negative-Sense RNA Viruses ; RNA Polymerase II ; Mammals
Chemical Substances	RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001963
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Article ; Online: Comment: Mis-Genotyping of Some Hepatitis D Virus Genotype 2 and 5 Sequences Using HDVdb.

Charre, Caroline / le Gal, Frédéric / Dény, Paul / Scholtès, Caroline

Viruses

2020 Volume 12, Issue 10

Abstract: Evidence that Hepatitis D virus (HDV) genotype is involved in HDV infection pathogenesis is increasing. Indeed, HDV genotypes have been shown to be linked to different outcomes in terms of liver fibrosis and treatment response. Herein, we show that the ... ...

Abstract	Evidence that Hepatitis D virus (HDV) genotype is involved in HDV infection pathogenesis is increasing. Indeed, HDV genotypes have been shown to be linked to different outcomes in terms of liver fibrosis and treatment response. Herein, we show that the promising HDVdb genotyping tool available online can lead to wrong genotyping results. The current HDVdb algorithm should be carefully considered as a "beta-version" and warrants algorithm core corrections, as soon as possible, for an optimal and beneficial use.
MeSH term(s)	Computational Biology ; Databases, Nucleic Acid ; Genotype ; Genotyping Techniques ; Hepatitis Delta Virus/genetics ; Phylogeny ; Sequence Analysis, RNA
Language	English
Publishing date	2020-09-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12101066
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Article: Mis-Genotyping of Some Hepatitis D Virus Genotype 2 and 5 Sequences Using HDVdb

Charre, Caroline / le Gal, Frédéric / Dény, Paul / Scholtès, Caroline

Viruses. 2020 Sept. 23, v. 12, no. 10

2020

Abstract	Evidence that Hepatitis D virus (HDV) genotype is involved in HDV infection pathogenesis is increasing. Indeed, HDV genotypes have been shown to be linked to different outcomes in terms of liver fibrosis and treatment response. Herein, we show that the promising HDVdb genotyping tool available online can lead to wrong genotyping results. The current HDVdb algorithm should be carefully considered as a “beta-version” and warrants algorithm core corrections, as soon as possible, for an optimal and beneficial use.
Keywords	Hepatitis delta virus ; algorithms ; genotype ; genotyping ; liver cirrhosis ; pathogenesis
Language	English
Dates of publication	2020-0923
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12101066
Database	NAL-Catalogue (AGRICOLA)

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Book: Virus de l'hépatite C

Deny, Paul

(Guides médi/bio,)

2003

Author's details	coordinateurs, Paul Dény, Dominique Roulot
Series title	Guides médi/bio,
MeSH term(s)	Hepatitis C ; Hepacivirus
Language	French
Size	190 p.
Publisher	Elsevier
Publishing place	Paris
Document type	Book
ISBN	9782842994471 ; 2842994477
Database	Catalogue of the US National Library of Medicine (NLM)

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Article: Comprehensive Analysis of Hepatitis Delta Virus Assembly Determinants According to Genotypes: Lessons From a Study of 526 Hepatitis Delta Virus Clinical Strains.

Gerber, Athenaïs / Le Gal, Frédéric / Dziri, Samira / Alloui, Chakib / Roulot, Dominique / Dény, Paul / Sureau, Camille / Brichler, Ségolène / Gordien, Emmanuel

Frontiers in microbiology

2021 Volume 12, Page(s) 751531

Abstract: Human hepatitis Delta virus (HDV) infection is associated to the most severe viral hepatic disease, including severe acute liver decompensation and progression to cirrhosis, and hepatocellular carcinoma. HDV is a satellite of hepatitis B virus (HBV) that ...

Abstract	Human hepatitis Delta virus (HDV) infection is associated to the most severe viral hepatic disease, including severe acute liver decompensation and progression to cirrhosis, and hepatocellular carcinoma. HDV is a satellite of hepatitis B virus (HBV) that requires the HBV envelope proteins for assembly of HDV virions. HDV and HBV exhibit a large genetic diversity that extends, respectively to eight (HDV-1 to -8) and to ten (HBV/A to/J) genotypes. Molecular determinants of HDV virion assembly consist of a C-terminal Proline-rich domain in the large Hepatitis Delta Antigen (HDAg) protein, also known as the Delta packaging domain (DPD) and of a Tryptophan-rich domain, the HDV matrix domain (HMD) in the C-terminal region of the HBV envelope proteins. In this study, we performed a systematic genotyping of HBV and HDV in a cohort 1,590 HDV-RNA-positive serum samples collected between 2001 to 2014, from patients originated from diverse parts of the world, thus reflecting a large genetic diversity. Among these samples, 526 HBV (HBV/A, B, C, D, E, and G) and HDV (HDV-1, 2, 3, and 5 to -8) genotype couples could be obtained. We provide results of a comprehensive analysis of the amino-acid sequence conservation within the HMD and structural and functional features of the DPD that may account for the yet optimal interactions between HDV and its helper HBV.
Language	English
Publishing date	2021-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.751531
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Article: Variable In Vivo Hepatitis D Virus (HDV) RNA Editing Rates According to the HDV Genotype

Dziri, Samira / Rodriguez, Christophe / Gerber, Athenaïs / Brichler, Ségolène / Alloui, Chakib / Roulot, Dominique / Dény, Paul / Pawlotsky, Jean Michel / Gordien, Emmanuel / Le Gal, Frédéric

Viruses. 2021 Aug. 09, v. 13, no. 8

2021

Abstract: Human hepatitis delta virus (HDV) is a small defective RNA satellite virus that requires hepatitis B virus (HBV) envelope proteins to form its own virions. The HDV genome possesses a single coding open reading frame (ORF), located on a replicative ... ...

Abstract	Human hepatitis delta virus (HDV) is a small defective RNA satellite virus that requires hepatitis B virus (HBV) envelope proteins to form its own virions. The HDV genome possesses a single coding open reading frame (ORF), located on a replicative intermediate, the antigenome, encoding the small (s) and the large (L) isoforms of the delta antigen (s-HDAg and L-HDAg). The latter is produced following an editing process, changing the amber/stop codon on the s-HDAg-ORF into a tryptophan codon, allowing L-HDAg synthesis by the addition of 19 (or 20) C-terminal amino acids. The two delta proteins play different roles in the viral cell cycle: s-HDAg activates genome replication, while L-HDAg blocks replication and favors virion morphogenesis and propagation. L-HDAg has also been involved in HDV pathogenicity. Understanding the kinetics of viral editing rates in vivo is key to unravel the biology of the virus and understand its spread and natural history. We developed and validated a new assay based on next-generation sequencing and aimed at quantifying HDV RNA editing in plasma. We analyzed plasma samples from 219 patients infected with different HDV genotypes and showed that HDV editing capacity strongly depends on the genotype of the strain.
Keywords	Hepatitis B virus ; Hepatitis delta virus ; RNA ; amber ; antigens ; cell cycle ; genotype ; hepatitis ; humans ; morphogenesis ; natural history ; pathogenicity ; satellite viruses ; stop codon ; tryptophan ; virion
Language	English
Dates of publication	2021-0809
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081572
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The hepatitis D satellite virus of hepatitis B virus: half-opening a new era to control viral infection?

Abeywickrama-Samarakoon, Natali / Cortay, Jean-Claude / Dény, Paul

Current opinion in infectious diseases

2016 Volume 29, Issue 6, Page(s) 645–653

Abstract: Purpose of review: To highlight new concepts and therapeutic approaches concerning hepatitis D virus (HDV) infection.: Recent findings: Common receptor for hepatitis B virus (HBV) and HDV has been elucidated, deciphering of HDV replication is still ... ...

Abstract	Purpose of review: To highlight new concepts and therapeutic approaches concerning hepatitis D virus (HDV) infection. Recent findings: Common receptor for hepatitis B virus (HBV) and HDV has been elucidated, deciphering of HDV replication is still in progress, preliminary results of phase II proof-of-concept clinical assays for entry inhibitors and cellular farnesyl transferase inhibitors are now available. Summary: Hepatitis D infection remains a severe acute and chronic liver illness with the only currently approved therapy (Peg-αIFN) achieving disappointingly low rates of sustained viral response and clinical improvement. Both sodium taurocolate cotransporting polypeptide and heparan sulphate glypican 5 are important for viral adsorption. Preliminary results of 6 months treatment with a subcutaneous HBV PreS1-derived myristoyled peptide as an entry inhibitor indicates an encouraging short-term response with low side-effects. In addition, the short-term use of oral farnesyl transferase inhibitors induces a log10 reduction of viral RNA in almost all treated patients, but is associated with gastrointestinal upset and weight loss (especially using 200 mg/day). Encouraging results are being reported using intravenous phosphorothioate nucleic acid polymers both in terms of HBV surface antigens (HBsAg) and HDV-RNA decline; interestingly, in some patients with a strong HBsAg decline, the appearance of anti-hepatitis Bs antibodies might suggest clinical end-point improvement.
MeSH term(s)	Enzyme Inhibitors/therapeutic use ; Farnesyltranstransferase/antagonists & inhibitors ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/immunology ; Hepatitis D/drug therapy ; Hepatitis D/virology ; Hepatitis Delta Virus/immunology ; Humans ; Satellite Viruses
Chemical Substances	Enzyme Inhibitors ; Hepatitis B Surface Antigens ; Farnesyltranstransferase (EC 2.5.1.29)
Language	English
Publishing date	2016-10-15
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000321
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Article ; Online: A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes.

Philippon, Alain / Slama, Patrick / Dény, Paul / Labia, Roger

Clinical microbiology reviews

2016 Volume 29, Issue 1, Page(s) 29–57

Abstract: For medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for ...

Abstract	For medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for data concerning class A β-lactamases, a group of key antibiotic resistance enzymes produced by bacteria. Many genomes have been reported to contain putative β-lactamase genes, which can be compared with representative types. We analyzed several hundred amino acid sequences of class A β-lactamase enzymes for phylogenic relationships, the presence of specific residues, and cluster patterns. A clear distinction was first made between dd-peptidases and class A enzymes based on a small number of residues (S70, K73, P107, 130SDN132, G144, E166, 234K/R, 235T/S, and 236G [Ambler numbering]). Other residues clearly separated two main branches, which we named subclasses A1 and A2. Various clusters were identified on the major branch (subclass A1) on the basis of signature residues associated with catalytic properties (e.g., limited-spectrum β-lactamases, extended-spectrum β-lactamases, and carbapenemases). For subclass A2 enzymes (e.g., CfxA, CIA-1, CME-1, PER-1, and VEB-1), 43 conserved residues were characterized, and several significant insertions were detected. This diversity in the amino acid sequences of β-lactamases must be taken into account to ensure that new enzymes are accurately identified. However, with the exception of PER types, this diversity is poorly represented in existing X-ray crystallographic data.
MeSH term(s)	Bacteria/enzymology ; Crystallography, X-Ray ; Genetic Variation ; Genotype ; Phylogeny ; Protein Conformation ; Structure-Activity Relationship ; beta-Lactamases/chemistry ; beta-Lactamases/classification ; beta-Lactamases/genetics ; beta-Lactamases/metabolism
Chemical Substances	beta-Lactamases (EC 3.5.2.6)
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.00019-15
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Article ; Online: Hepatitis delta virus: From biological and medical aspects to current and investigational therapeutic options.

Alfaiate, Dulce / Dény, Paul / Durantel, David

Antiviral research

2015 Volume 122, Page(s) 112–129

Abstract: An estimated 15-20 million individuals are co-infected by hepatitis B and hepatitis D virus worldwide and are at high risk of developing end-stage liver disease, including hepatocellular carcinoma. While HBV viremia can now be controlled in the vast ... ...

Abstract	An estimated 15-20 million individuals are co-infected by hepatitis B and hepatitis D virus worldwide and are at high risk of developing end-stage liver disease, including hepatocellular carcinoma. While HBV viremia can now be controlled in the vast majority of individuals by nucleoside analogs, leading to a delay of disease progression, HDV treatment has for long relied on the relatively inefficient and not well-tolerated interferon-alpha. While the epidemiology and pathogenesis of the disease remain to be precisely determined, using adequate diagnostic tools and well-designed cohort studies, basic research efforts have led to interesting progress in the understanding of HDV biology, which is not yet sufficient to identify specific antiviral targets. More resources now need to be devoted to the HDV field to achieve therapeutic breakthroughs. In this manuscript, we carefully review the literature regarding the biology of hepatitis D virus, the disease, its prevention, current treatments and investigational strategies. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B."
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/virology ; Coinfection/therapy ; Coinfection/virology ; Hepatitis B/complications ; Hepatitis B/drug therapy ; Hepatitis B virus/physiology ; Hepatitis D, Chronic/drug therapy ; Hepatitis D, Chronic/epidemiology ; Hepatitis D, Chronic/virology ; Hepatitis Delta Virus/drug effects ; Hepatitis Delta Virus/physiology ; Humans ; Liver Neoplasms/therapy ; Liver Neoplasms/virology ; Molecular Epidemiology ; Viral Interference ; Virus Assembly ; Virus Release ; Virus Replication
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2015-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2015.08.009
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