A5030576100- Hepatitis B Virus Studies
- Hepatitis C virus research
- Viral gastroenteritis research and epidemiology
- Bacteriophages and microbial interactions
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Hepatitis Viruses Studies and Epidemiology
- Advanced NMR Techniques and Applications
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- NMR spectroscopy and applications
- Vector-borne infectious diseases
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Photosynthetic Processes and Mechanisms
- Toxin Mechanisms and Immunotoxins
- Advanced MRI Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Click Chemistry and Applications
University Medical Center Freiburg
2015-2024
University of Freiburg
2005-2023
Heidelberg University
1989-2010
Chirurgische Universitätsklinik Heidelberg
2010
University Hospital Heidelberg
1999-2010
DKFZ-ZMBH Alliance
1993
German Cancer Research Center
1993
Massachusetts Institute of Technology
1973-1987
University of New Brunswick
1987
Istituto di Genetica Molecolare
1987
Assembly of replication-competent hepatitis B virus (HBV) nucleocapsids requires the interaction core protein, P and RNA pregenome. The protein contains an arginine-rich C-terminal domain which is dispensable for particle formation in heterologous expression systems. Using transient HuH7 cells a series C-terminally truncated proteins, I examined functional role this basic region context complete HBV genome. All variants containing at least 144 N-terminal amino acids were assembly competent,...
As a step toward understanding the assembly of hepatitis B virus (HBV) nucleocapsid at molecular level, we sought to define primary sequence requirements for HBV core protein. This protein can self assemble upon expression in Escherichia coli. Applying this system series C-terminally truncated variants, mapped C-terminal limit region between amino acid residues 139 and 144. The size domain agrees well with minimum length RNA capsid proteins that fold into an eight-stranded beta-barrel...
Significance Chronic hepatitis B virus (HBV) infection puts >250 million humans at risk for developing liver cirrhosis and cancer. Current therapies are not curative because they do target HBV´s persistence reservoir, the plasmid-like covalently closed circular DNA (cccDNA). RNA production from cccDNA initiates generation of progeny via protein-primed reverse transcription, yielding viral polymerase-linked relaxed-circular (RC-DNA). Its conversion, upon infection, into requires multiple...
The nucleocapsid of hepatitis B virus (HBV), or HBcAg, is a highly symmetric structure formed by multiple dimers single core protein that contains potent T helper epitopes in its 183-aa sequence. Both factors make HBcAg an unusually strong immunogen and attractive candidate as carrier for foreign epitopes. immunodominant c/e1 epitope on the capsid has been suggested superior location to convey high immunogenicity heterologous Because central position, however, any insert disrupts protein’s...
To carry out systematic structure-function studies of bovine rhodopsin by specific amino acid replacements, we have accomplished the total synthesis its gene, which is 1057 base pairs long. The synthetic gene contains 28 unique restriction sites that are on average 60 apart. Replacement fragments counterparts containing desired nucleotide changes permits mutagenesis in all parts gene. involved enzymatic joining a 72 oligonucleotides, 15-40 nucleotides long, to form DNA duplexes. was...
Chronic hepatitis B and D infections are major causes of liver disease hepatocellular carcinoma worldwide. Efficient therapeutic approaches for cure absent. Sharing the same envelope proteins, virus delta use sodium/taurocholate cotransporting polypeptide (a bile acid transporter) as a receptor to enter hepatocytes. However, detailed mechanisms viral entry process still poorly understood. Here, we established high-throughput infectious cell culture model enabling functional genomics...
A critical feature of a viral life cycle is the ability to selectively package genome. In vivo, phosphorylated hepatitis B virus (HBV) core protein specifically encapsidates complex pregenomic RNA (pgRNA) and polymerase; it has been suggested that packaging specific for complex. Here, we test hypothesis intrinsic specificity pgRNA, independent polymerase. For these studies, also evaluated effect phosphorylation on assembly binding, using mimic in which S155, S162, S170 were mutated glutamic...
Coinfection with hepatitis B virus (HBV) and C (HCV) has been associated severe liver disease frequent progression to cirrhosis hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV HCV have difficult study due lack appropriate model systems. We established a novel system investigate HCV. Stable Huh-7 cell lines inducibly replicating were transfected selectable replicons infected...
Objective A hallmark of chronic HBV (cHBV) infection is the presence impaired HBV-specific CD8+ T cell responses. Functional exhaustion induced by persistent antigen stimulation considered a major mechanism underlying this impairment. However, due to their low frequencies in infection, it currently unknown whether cells targeting different epitopes are similarly and share molecular profiles indicative exhaustion. Design By applying peptide-loaded MHC I tetramer-based enrichment, we could...
Persistence of hepatitis B virus (HBV) infection requires covalently closed circular (ccc)DNA formation and amplification, which can occur via intracellular recycling the viral polymerase-linked relaxed (rc) DNA genomes present in virions. Here we reveal a fundamental difference between HBV related duck (DHBV) mechanism. Direct comparison DHBV cccDNA amplification cross-species transfection experiments showed that, same human cell background, but not rcDNA converts efficiently into cccDNA....
Progress in NMR general and biomolecular applications particular is driven by increasing magnetic-field strengths leading to improved resolution sensitivity of the spectra. Recently, persistent superconducting magnets at a magnetic field strength (magnetic induction) 28.2 T corresponding 1200 MHz proton resonance frequency became commercially available. We present here collection high-field spectra variety proteins, including molecular machines, membrane viral capsids, fibrils large...
ABSTRACT The Asian tree shrew, Tupaia belangeri , has been proposed as a novel animal model for studying hepatitis B virus (HBV) infection. Here, we describe protocol efficient and reproducible infection of primary tupaia hepatocytes with HBV. We report that human serum interferes HBV binding to the hepatocytes, thus limiting maximum multiplicity Purification virions by gradient sedimentation greatly enhances infectivity. Covalently closed circular DNA was clearly detectable Southern blot...
Human hepatitis B virus (HBV) is a small DNA that replicates inside the viral nucleocapsid by reverse transcription of an RNA intermediate. Encapsidation this pregenome mediated interaction replication enzyme P with structured 5'-proximal element epsilon; was thought to start in 3'-proximal direct repeat DR1*. However, recent data obtained duck indicated novel, discontinuous mechanism negative-strand synthesis. Here we demonstrate, using transfection complete HBV genomes, 3'-half...
Hepatitis B virus (HBV) is the type member of hepadnaviridae, small enveloped DNA viruses that replicate through reverse transcription an RNA intermediate, pregenome. This reaction occurs usually inside viral nucleocapsid, assembly which requires specific interactions between multiple copies core protein, replication enzyme (P protein) and pregenome also serves as mRNA for both proteins. Deletion studies have established packaging mediated by a short cis-acting sequence, encapsidation signal...