A5062644021- Hepatitis B Virus Studies
- Hepatitis C virus research
- Drug Transport and Resistance Mechanisms
- Hepatitis Viruses Studies and Epidemiology
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Immunotherapy and Immune Responses
- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
- Toxin Mechanisms and Immunotoxins
- HIV/AIDS drug development and treatment
- Natural product bioactivities and synthesis
- Molecular Biology Techniques and Applications
German Center for Infection Research
2018-2024
Justus-Liebig-Universität Gießen
2018-2024
Abstract Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding viral surface polypeptide preS1 to hepatobiliary transporter Na + -taurocholate co-transporting (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a derivative approved drug for treating HDV infection. Here, elucidate basis this inhibitory function, we determined cryo-EM structure BLV-bound human NTCP. BLV forms two domains, plug lodged in bile salt transport tunnel NTCP...
Highlights•A divergent HBV species termed CMHBV was discovered in Brazilian capuchin monkeys.•CMHBV and the related WMHBV use same receptor as to infect human cells.•CMHBV may cause chronic hepatitis B, potentially enabling new animal models.•Primates have been carrying HBV-related viruses for millions of years.•New World genotypes were likely introduced during peopling Americas.Graphical abstractAbstractBackground & AimsAll known B virus (HBV) occur humans hominoid Old non-human primates...
Significance Hepatitis delta virus (HDV) aggravates hepatitis B (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires envelope protein for its transmission. is only described in humans, which has triggered diverse hypotheses regarding evolution and origins. Here we show that spiny rats ( Proechimys semispinosus ) carry a counterpart to surprisingly does not cause linked HBV. The rodent deltavirus finding alone, but also...
Abstract Current treatment options against hepatitis B and D virus (HBV/HDV) infections have only limited curative effects. Identification of Na + /taurocholate co-transporting polypeptide (NTCP) as the high-affinity hepatic receptor for both viruses in 2012 enables target-based development HBV/HDV cell-entry inhibitors. Many studies already identified appropriate NTCP However, most them interfere with NTCP’s physiological function a bile acid transporter. To overcome this drawback, present...
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for hepatitis B D viruses (HBV/HDV). Virus entry via endocytosis of virus/NTCP complex involves co-factors, but this process not fully understood. As part innate immunity, interferon-induced transmembrane proteins (IFITM) 1-3 have been characterized as virus entry-restricting factors many viruses. present study identified IFITM3...
The recent discovery of Hepatitis D (HDV) -like viruses across a wide range taxa led to the establishment Kolmioviridae family. Recent studies suggest that kolmiovirids can be satellites other than B virus (HBV), challenging strict HBV/HDV-association dogma. Studying whether are able replicate in any animal cell they enter is essential assess their zoonotic potential. Here, we compared replication three kolmiovirids: HDV, rodent (RDeV) and snake (SDeV) deltavirus vitro vivo . We show SDeV...
Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs C virus (HCV). Because coinfections (HBV) and HCV occur in humans, we screened 2,917 specimens from equids five continents HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) 3.2% donkeys zebras by PCR antibodies against EqHBV 5.4% zebras. Molecular, histopathological, biochemical analyses revealed that infection patterns resembled those including...
Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic range. The phylogenetically divergent shrew comprise separate species termed crowned HBV (CSHBV) musk (MSHBV), each containing distinct genotypes. Recombination events orders, evolutionary reconstructions, antigenic divergence...
Currently available HDV PCR assays are characterized by considerable run-to-run and inter-laboratory variability. Hence, we established a quantitative reverse transcription real-time (RT-qPCR) assay on the open channel of fully automated platform (cobas6800, Roche) offering improved consistency reliability.A primer/probe-set targeting highly conserved region upstream antigen was adapted for use cobas6800. The lower limit detection (LLOD) determined using dilution panel WHO standard (n =...
The hepatic bile acid transporter Na+/taurocholate co-transporting polypeptide (NTCP) was identified in 2012 as the high-affinity receptor for hepatitis B and D viruses (HBV/HDV). Since then, this carrier has emerged promising drug target HBV/HDV virus entry inhibitors, but synthetic peptide Hepcludex® of high molecular weight is only approved HDV inhibitor so far. present study aimed to identify small molecules novel NTCP inhibitors with anti-viral activity. A ligand-based bioinformatic...
Pegylated interferon alpha (pegIFNα) is commonly used for the treatment of people infected with HDV. However, its mode action in HDV-infected cells remains elusive and only a minority respond to pegIFNα therapy. Herein, we aimed assess responsiveness three different cloned HDV strains pegIFNα. We previously genotype 1 strain (dubbed HDV-1a) that appeared insensitive interferon-α vitro, new (HDV-1p) isolated from an individual achieving later sustained response IFNα therapy, one...
Human hepatic bile acid transporter Na+/taurocholate cotransporting polypeptide (NTCP) represents the liver-specific entry receptor for hepatitis B and D viruses (HBV/HDV). Chronic affect several million people worldwide, but treatment options are limited. Recently, HBV/HDV inhibitors targeting NTCP have emerged as promising novel drug candidates. Nevertheless, exact molecular mechanism that uses to mediate virus binding into hepatocytes is still not completely understood. It already known...
Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of acids. Apart from its transporter function, NTCP acts as high-affinity liver-specific receptor for hepatitis B virus (HBV), which attaches via preS1-peptide domain large surface protein to NTCP, subsequently leading endocytosis virus/NTCP-receptor complex. Although process NTCP-dependent HBV infection hepatocytes has received much...
Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes binding site HBV to its receptor on hepatocytes. We investigated if non-responsiveness after repeated vaccinations can be overcome by immunization VVX001 (i.e., Alum-adsorbed BM325, component BM32). Methods: A subject...
Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as high-affinity hepatic entry receptor for the Hepatitis B and D viruses (HBV/HDV) opened field target-based development cell-entry inhibitors. However, most HBV/HDV inhibitors identified so far also interfere with physiological bile acid transporter function NTCP. The present study aimed to identify more virus-selective NTCP by screening 87 propanolamine derivatives from former intestinal reabsorption (BARIs), which...
Homodimerization is essential for plasma membrane sorting of the liver bile acid transporter NTCP and its function as Hepatitis B/D Virus (HBV/HDV) receptor. However, protein domains involved in dimerization are unknown. bears two potential GXXXG/A motifs transmembrane (TMDs) 2 7. The present study aimed to analyze role these sorting, function, NTCP. mutants G 60 LXXXA 64 L (TMD2), 233 LXXXG 237 (TMD7) a double mutant were generated analyzed their interaction with wild-type using...
<h3></h3> A2342 is a novel small-molecule, orally available, selective inhibitor of hepatic transporter Na+/taurocholate co-transporting polypeptide (NTCP). NTCP mediates uptake bile acids into hepatocytes and acts as host receptor for hepatitis B D viruses (HBV/HDV). The preS1 domain the large envelope protein HBV/HDV essential binding these virus particles to NTCP. We previously demonstrated that lowers HBV DNA viral load in infected human vitro also attenuates antigens humanized mice...
Cellular entry of the hepatitis B and D viruses (HBV/HDV) require binding viral surface polypeptide preS1 to hepatobiliary transporter NTCP. This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a derivative approved drug for treating HDV infection. To elucidate basis this inhibitory function, we determined cryo-EM structure BLV-bound human BLV forms two domains, plug lodged in bile salt transport tunnel NTCP string that covers receptors extracellular surface. The...
Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as an immunological carrier protein. PreS includes binding site HBV to its receptor on hepatocytes. We investigated whether non-responsiveness after repeated vaccinations could be overcome by immunization VVX001 (i.e., alum-adsorbed BM325, component BM32).
Question Hepatitis Delta Virus (HDV) is a negative strand circular RNA virus with strong self-base-pairing and high diversity between the 8 known genotypes (GT). Both of these features pose considerable challenge for diagnostic workflows many available PCR assays are characterized by run to inter-laboratory variability. The aim study was establish quantitative real-time assay on open channel fully automated platform (cobas6800, Roche) offering improved consistency reliability.
Abstract The recent discovery of Hepatitis D (HDV) -like viruses across a wide range taxa led to the establishment Kolmioviridae family. Recent studies suggest that kolmiovirids can be satellites other than B virus (HBV), challenging strict HBV/HDV-association dogma. Studying whether are able replicate in any animal cell they enter is essential assess their zoonotic potential. Here, we compared replication three kolmiovirids: HDV, rodent (RDeV) and snake deltavirus (SDeV) vitro vivo . We...
Background HBV evolution, diversity and phylogeographic history remain unclear. The successful retrieval of DNA from archaeological human remains allows genotypic phenotypic studies lineages over thousands years. Aim this study was to generate, clone characterize the infectivity a 1,160-years-old isolate genotype D (GT-D, DA222) in vitro vivo.