Search results for "PRECURSOR"
showing 10 items of 490 documents
Behavior of a Short preS1 Epitope on the Surface of Hepatitis B Core Particles
1999
The major immunodominant region of hepatitis B core particles is widely recognized as the most prospective target for the insertion of foreign epitopes, ensuring their maximal antigenicity and immunogenicity. This region was mapped around amino acid residues 79-81, which were shown by electron cryo-microscopy to be located on the tips of the spikes protruding from the surface of hepatitis B core shells. Here we tried to expose a model sequence, the short immunodominant hepatitis B preS1 epitope 31-DPAFR-35, onto the tip of the spike, with simultaneous deletion of varying stretches from the major immunodominant region of the HBc molecule. Accessibility to the monoclonal anti-preS1 antibody M…
Mosaic hepatitis B virus core particles presenting the complete preS sequence of the viral envelope on their surface
2004
The sequence of the preS domain of the hepatitis B virus (HBV, genotype D) envelope was inserted into the major immunodominant region (MIR) of the C-terminally truncated HBV core (HBc) protein. In Escherichia coli, the HBc–preS fusion protein was partially soluble and did not produce particles. Co-expression of the wild-type HBc as a helper protein along with the fusion protein led to the formation of mosaic HBc particles that exhibited HBc, preS1 and preS2 antigenicity. Two alternative combinations of medium- and high-copy plasmids were used for co-expression of fusion and helper proteins, in an attempt to improve mosaic particle production. However, the preS fusion content of the particle…
N-terminal myristoylation-dependent masking of neutralizing epitopes in the preS1 attachment site of hepatitis B virus
2011
The N-terminally myristoylated preS1 domain of the large hepatitis B surface protein (LHBs) mediates specific attachment of hepatitis B virus (HBV) to hepatocytes. Its B-cell epitopes leading to neutralization of infectivity are not yet characterized.We inserted C- and N-terminal preS1 peptides into the most immunogenic region of HBV core particles, therewith immunized Balb/c mice and determined binding properties and neutralization potential of resulting antibodies in vitro.The particles with preS1 inserts were highly immunogenic and the corresponding anti-preS antibodies strongly bound to HBV particles from chronic carriers infected with different HBV genotypes A-F. However, antibodies bi…
Expression of Pre-S-Encoded Proteins in Sera of Individuals Chronically Infected with Hepatitis D Virus
1988
The sera of 16 individuals chronically infected with the hepatitis D virus were analyzed for hepatitis B virus (HBV) markers. The majority of these patients had a non-replicative form of viral type B hepatitis as indicated by negative tests for HBeAg and HBV-DNA. Pre-S-encoded proteins were detected in 13/16 sera. Sera that were negative for polymerized serum albumin did also not contain pre-S1-encoded proteins. The presence of pre-S-encoded proteins is probably predominantly associated with 22-nm HBsAg forms present in large amounts in sera of individuals with chronic type D hepatitis.
Chaperones Involved in Hepatitis B Virus Morphogenesis
1999
Little is known about host cell factors necessary for hepatitis B virus (HBV) assembly which involves envelopment of cytosolic nucleocapsids by the S, M and L transmembrane viral envelope proteins and subsequent budding into intraluminal cisternae. Central to virogenesis is the L protein that mediates hepatocyte receptor binding and envelopment of capsids. To serve these topologically conflicting roles, L protein exhibits an unusual dual membrane topology, disposing its N-terminal preS domain inside and outside of the virion lipid envelope. The mixed topology is achieved by posttranslational preS translocation of about half of the L protein molecules across a post-endoplasmic reticulum memb…
Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation.
1996
Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240…
Possible role of human interleukin-6 and soluble interleukin-6 receptor in hepatitis B virus infection
2001
Human interleukin-6 has been shown to promote hepatitis B virus (HBV) infection. However, it is not clear whether this influence is the result of a direct interaction between interleukin-6 (IL-6) and the HBV envelope proteins or of a rather indirect mechanism. A direct interaction of IL-6 and the preS region of the large envelope protein (L-protein) of HBV has been reported. In this study we assessed the binding of IL-6 and of the IL-6 receptor subunits to the preS region of the L-protein of HBV. Binding of IL-6 and IL-6 receptor subunits sIL-6R and gp130 to preS was assessed by immunoprecipitation with recombinant preS proteins. In patient sera IL-6 and sIL-6R concentrations were analysed …
Myristylation is involved in intracellular retention of hepatitis B virus envelope proteins
1991
The envelope of hepatitis B virus contains three related proteins, one of which is myristylated. The nonmyristylated small and middle protein are assembled into empty envelope particles which are secreted from cells, whereas the myristylated large envelope protein is mainly found in complete virions and is not secreted in the absence of the nucleocapsid. The block to secretion can be partially overcome by mutation or deletion of the myristylation site. Creation of a myristyl attachment site in the small protein impairs the secretion of empty envelope particles but not their intracellular assembly. Myristylation may therefore play a crucial role in hepatitis B virus replication by channeling…
A Versatile Approach to CF3-Containing 2-Pyrrolidones by Tandem Michael Addition-Cyclization: Exemplification in the Synthesis of Amidine Class BACE1…
2015
The synthesis of new fluorinated pyrrolidones starting from unprotected amino esters and amino nitriles through a Michael addition-lactamization sequence is described. The resulting CF3 -containing building blocks, bearing a quaternary stereogenic center adjacent to the fluorinated group, have been converted into amino pyrrolidines that display potent β-secretase 1 (BACE1) inhibitory activity. This work constitutes an example of selective fluorination as a valid strategy for the modulation of physicochemical and biological properties of lead compounds in drug discovery.
Study of the effect of H2S, MeSH and DMS on the sensory profile of wine model solutions by Rate-All-That-Apply (RATA)
2016
The effect of hydrogen sulfide (HS), methanethiol (MeSH) and dimethyl sulfide (DMS) on the odor properties of three wine models-WM- (young white, young red and oaked red wines) was studied. Wine models were built by mixing a pool of common wine volatile and non-volatile compounds and further spiked with eight different combinations of the three sulfur compounds present at two levels (level 0: 0 μg L and level 1: 40 μg L of HS, 12 μg L of MeSH; 55 μg L of DMS). For each wine matrix eight WMs were produced and further submitted to sensory description by Rate-All-That-Apply (RATA) method. Hydrogen sulfide and methanethiol were clearly involved in the formation of reductive aromas and shared th…