hepatitis delta antigens

..These results suggested that phosphorylation of S-HDAg, with serine 177 as a presumable site, plays a critical role in viral RNA replication, especially in augmenting the replication of antigenomic RNA...

..These data indicate a critical role of NESI in the assembly of HDV through interaction with HDAg-L...

..This suggests that HDV RNA mediates export of viral particles to the cytoplasm whereas the delta antigen triggers their reimport into the nucleus...

..Deletion and mutation analysis of this region showed that both the acidic glutamic acid residue at position 66 and the basic arginine residue at position 75 are essential for promoting nuclear import...

..Therefore, this work demonstrates the important role of nucleolar protein in regulating the HDV RNA replication through the complex formation with the key positive regulator being small HDAg...

..It starts with a brief overview of HDV and its replication, notes some of the major unresolved questions, and directs the interested reader to more detailed reviews...

..These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication...

..These results indicate that HDAg-L is a new clathrin adaptor-like protein, and it may be involved in the maturation and pathogenesis of HDV coinfection or superinfection with hepatitis B virus through interaction with clathrin...

..These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication...

..These results bring the geographic distribution of HDV closer to the genetic variability of its helper HBV...

....

..Other than human immunodeficiency virus type 1 trans-activating protein (Tat), S-HDAg is another viral protein phosphorylated by PKR that may regulates HDV replication and viral response to interferon therapy...

..These results demonstrate the role of ERK1/2-mediated Ser-177 phosphorylation in modulating HDV antigenomic RNA replication, possibly through RNAPII regulation. The results may shed light on the mechanisms of HDV RNA replication...

..Furthermore, assembly of HDV is insensitive to leptomycin B, indicating that the NES(HDAg-L) directs nuclear export of HDAg-L to the cytoplasm via a chromosome region maintenance 1-independent pathway...

..In addition, the structure adjacent to the amber/W site is suboptimal for editing, and this creates a window of time in which replication can occur in the absence of HDAg-L...

....

..These observations demonstrate that a host gene product can modulate HDV replication and suggest that HDV may have evolved from a primitive viroidlike RNA through capture of a cellular transcript...

..Thus, the current study demonstrated that both cis and trans elements modulate HDAg translocation to various subcellular sites...

....

..Nevertheless, TNF-alpha-induced GFP-LD translocation was independent of new protein synthesis, suggesting that a post-translational event occurs to GFP-LD to allow translocation...

..All together, our results reveal that HDAg interacts with cellular transcription factor YY1 and its associated acetyltransferases CBP and p300 in a large nuclear complex, which in turn modulates the replication of HDV RNA...

..Findings include evidence that HDV replication is somehow able to direct the available delta antigen to sites in the nucleoplasm, almost exclusively colocalized with Pol II in what others have described as transcription factories...

..In situ hybridization showing co-localization of HDV RNA with D(1-88)-GFP at nuclear speckles suggested that HDV RNA editing might occur in the nuclear speckles and require other nuclear factor(s), in addition to ADAR...

..In conclusion, genotype has no effect on HDAg interaction and genotype per se only partly predicts how much the HDAg-S of an HDV isolate affects the replication of a second HDV isolate...

..Apparently, for unit-length RNAs of HDV, PSTVd, and ASBVd, it is the extended structure with <100% base pairing that confers significant resistance to dicer action...

..The aim of this study was to define the natural long-term course of HDV compensated cirrhosis...

....

..This review covers the mechanisms of RNA editing in the HDV replication cycle and the regulatory mechanisms by which HDV controls editing...

..Analysis of obtained data showed that these peptides can be used in new diagnostic anti-HDV tests...

..2 g/cm3 in caesium chloride and approximately 1.15 g/cm3 in sucrose. The VLPs were also immunoprecipitated using an anti-HBs but not an anti-HD antibody. Thus, these recombinant VLPs have similar biophysical properties to L-HDAg VLPs...

..We propose that acetylation and deacetylation of HDAg may provide a molecular switch for the synthesis of the different HDV RNA species...

..Although the mutant protein was competent for interaction with and incorporation of free large hepatitis delta antigen, it was partially defective in hepatitis delta virus RNP incorporation...

..Treatment involves the administration of pegylated interferon-α and is effective in only about 20% of patients. Liver transplantation is indicated in case of liver failure...

..Thus, new strategies to develop a vaccine to prevent HDV superinfection are needed...

..This study defines several important protein-protein interactions and opens the way for understanding the mechanism of DSIF- and NELF-induced transcriptional pausing...

..These data indicated that HDV-induced clusterin protein increases cell survival potential. Thus, it is possible that epigenetic regulation by HDV contributes to a pathological outcome of hepatitis D/hepatitis B viral hepatitis and HCC...

..Chronic HDV infection in woodchucks may result from a delayed and weak immune response that is limited to a small number of epitopes on HDAg...

..Two RNA-positive/anti-HD-negative samples possessed a few uncommon nucleotide substitution sites within the L-HDAg sequence, which could suggest unique variants in the Polish population of HDV-infected patients...

..This review will cover the mechanisms of editing at the amber/W site and the means by which the virus controls it in these two genotypes...

..In order to ascertain the current status of HDV infection in Nigeria, a study of patients with hepatitis B virus (HBV)-related liver diseases was undertaken to determine the sero-prevalence ofanti-HDV...

..Heat-shock induction of HDAg expression revealed that L4 larvae were the most sensitive to brood size reduction. These studies demonstrate that C. elegans can provide an additional model for studying HDAg interactions with host targets...

..Our results indicate that the need of clinical and epidemiological studies to investigate the presence of this infection in other areas in Brazil...

..HuR was found to be overexpressed and colocalize with HDAg in human hepatoma cells. siRNA knockdown of HuR mRNA resulted in inhibition of S-HDAg and L-HDAg expression...

..Taken together, the baculovirus/mammalian cell system offers an attractive alternative for high level expression of L-HDAgH or other proteins that require extensive post-translational modifications...

..5, c = 63.5 A. The crystallization and X-ray analysis of multiple forms of the HDV RNA-editing substrate, encounters with common RNA crystal-growth defects and a strategy to overcome these problems are reported...

..The ability of mammalian cells to replicate HDV RNA implies that RNA-dependent RNA synthesis was preserved throughout evolution...

..The presence of Pro-205 in genotype 1 HDV may account for its higher assembly efficiencies and wider distribution...

..8% (between the Turkish isolates and HDV-1). The lowest sequence similarity is 56.4% (between the Turkish isolates and HDV-3). In conclusion, phylogenetic analysis shows that the Turkish HDV isolates belong to HDV-1...

..There is no cell line susceptible to hepatitis D virus (HDV) infection and capable of stable replication of its genome. Different genetic-based approaches have been introduced to initiate HDV replication events so far...

..Moreover, the down regulation of hnRNP D, HSP105, and triosephosphate isomerase was further confirmed by Real time PCR...

..By reducing transcriptional fidelity in terms of not only discrimination of incoming nucleotides but also recognition of templates, HDAg may facilitate the unusual RNA-dependent RNA synthesis by Pol II...

..The discovery of immunogenic epitopes, especially cytotoxic-T-lymphocyte ligands, associated with chronic HDV infection may be crucial for further development of novel treatments or designs in vaccine for HDV superinfection...

..6%), compared with previous Indian reports varying from 10.7% to >30%. HDV infection was relatively low and seems to play a minor determining factor of liver diseases in the tropical south Indian population...

..a peculiar form of fulminant hepatitis known as Labrea hepatitis, probably related to hepatitis B and D, has been reported in Brazilian Amazon as early as the 1930s...

..These agents represent a new class of antiviral agents, with HDV as a first target. Here, a brief review of the HDV life cycle emphasizing the role of prenylation is presented along with implications for drug development and therapy...

..The results are consistent with a model in which HDAg binds HDV unbranched rod RNA as multimers of fixed size rather than as individual subunits...

..These studies provide evidence that deltaAg does not interact directly with either Pol II or nucleolin and that forms of deltaAg which support replication are also capable of prior nucleolar transit...

..The results confirm the previous proposal that HDAg binds as a large multimer and demonstrate that the multimer is a critical determinant of the structure of the HDV RNP...

..However, unlike soluble forms of HBV envelope protein that were potent inhibitors, the SVP did not inhibit the ability of HBV and HDV to infect primary human hepatocytes...

....

..The role of the isoprenylated motif of hepatitis delta antigens (HDAg) in the generation of immune responses following DNA-based immunization has never been studied...

..Hence, the HDV amber/W site represents the smallest ADAR substrate yet identified. In contrast, the minimal substrate competent for hADAR2-mediated editing contained 66 nucleotides...

..We concluded that the HDV polyadenylation could be regulated by the structure of the nascent antigenomic RNA and by either the small or large HDAg...

....

..These results suggest that the genomic RNA species encoding S-HDAg is the only functional genome for HDV infection and explain why the presence of the edited HDV RNA encoding L-HDAg does not interfere with HDV infection...

..Therefore, in vivo, the C terminus likely provides an additional site of protein-protein interaction for the large delta antigen...

..Our results indicate that HDV requires highly regulated and selective editing and that the level of ADAR expression can play an important role: overexpression of ADARs inhibits HDV RNA replication and compromises virus viability...

..This phenomenon may be partly responsible for the persistent infection of chronic HDV patients...

..The anti-HDV assay may be useful for further epidemiological studies on HDV infection in larger cohorts in urban and rural areas of Mongolia, where elucidation of the transmission route of HDV is required urgently...

..These findings provide additional evidence that HDV RNA synthesis occurs in the Pol I and Pol II transcription machineries, thus extending the capability of the cellular DNA-dependent RNA polymerases to utilizing RNA as templates...

..To verify whether "defective" mutations existed in hepatitis D virus (HDV)...

..The different mechanisms of editing in genotypes I and III underscore their functional differences and may be related to pathogenic differences as well...

..e., HDV-I and HDV-III) rather than genotypes...

....

..Baculovirus can also be envisaged as a useful tool for investigating protein-cell interactions and virus assembly...

..It is believed that HDAg forms dimers and higher ordered structures through this coiled-coil region...

....

....

..Our results support the idea that the replication of HDV genomic RNA or antigenomic RNA is likely to be carried out by different machineries in different subcellular localizations...

..Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates NF-kappaB signaling pathway and may contribute to HDV pathogenesis...

..Thus, the clathrin box and the nuclear export signal at the C terminus of HDAg-L are potential new molecular targets for HDV therapy...

..Oligomers of purified δAg were resistant to elevated NaCl and urea concentrations, and bound without specificity to RNA and single- and double-stranded DNAs...

..There is no genotypic or size restriction on the interactions of either the small or the large hepatitis delta antigens (HDAgs) between genotypes I and II, and there is also no genotypic incompatibility during co-package of ..

..The described approach thus facilitates induction of serum antibody responses against native viral antigens with low immunogenicity for B cells...

..Mutations that reduce the RNA binding activity or high ionic strength that destabilizes the RNA-protein complex, reduce the nucleic acid chaperone activity of NdAg...

..We conclude that histone H1e plays a significant role in HDV replication through forming protein complex with SHDAg...

..The combination of baculovirus transduction and BelloCell reactor, thus, may represent a simple and efficient approach for the production of HDV VLP and viral vectors...

....

..Hepatitis D virus infection may induce the expression of bax in the hepatocytes and exacerbate hepatocyte apoptosis through which take a part in the pathogenesis of hepatitis D...

..These and other results suggest that hepatitis delta antigen may have a biological role as an RNA chaperone, modulating the folding of viral RNA for replication and transcription...

..We demonstrate its usage for localization of a bacterial virulence factor in host cells. This vector should be applicable for high-throughput characterization of new open reading frames found in genome sequencing...

..The aim of this study was to estimate the anti-delta prevalence in Koreans and to study the clinical characteristics of anti-delta positive patients in a single center...

..DNA vaccine with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV humoral immunity...

..Vaccination strategies tested in the woodchuck model induced specific B- and T-cell responses but failed to protect from HDV infection...

..Results are expected to be of fundamental interest to the RNA folding community and may impact the understanding of RNA folding in other biologically relevant RNA and RNA-protein systems including catalytic RNAs and the ribosome. ..

..Kinetic analysis of human RNAP II gives novel insight into the mechanism and regulation of translocation, NTP loading, pyrophosphate release and the efficiency and fidelity of NMP incorporation. ..

....

..These aims will be addressed by a combination of approaches, including site- directed mutagenesis, analysis in vitro of editing and RNA-protein interactions, and evaluation of editing and its consequences in transfected cells. ..

..We propose a combination of biophysical and functional studies that explore the importance of coiled-coil length and sequence for function of bacterial SMC proteins in vivo. ..

....

..In addition, these studies will also be crucial for translating the primary sequence of putative coiled-coil proteins into structural and functional information. ..

..We will use phage display to identify high affinity random peptide ligands of the AH. Finally, we will explore how our results can be translated into novel anti-HCV strategies. ..