Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier studies revealed that human interleukin 6 (IL-6) contains recognition sites for the hepatitis B virus (HBV) envelope (env) protein, and that IL-6 and anti-IL-6 antibodies, respectively, inhibited the interaction of cells expressing a receptor for HBV with the preS(21-47) segment of the HBV env protein, encompassing the complementary attachment site for IL-6. This suggested that IL-6 mediates HBV-cell interactions. We report that: (a) Chinese hamster ovary cells transfected with human IL-6 cDNA and Spodoptera frugiperda ovarian insect cells infected with recombinant baculovirus carrying human IL-6 cDNA expressed receptors for the preS(21-47) region of the HBV env protein, indicating that expression of IL-6 on the surface of cells is sufficient to endow them with receptors for HBV. (b) Among peptides covering the entire sequence of human IL-6 and the corresponding antipeptide antibodies, the peptide IL-6[35-66] and anti-IL-6[35-66] most effectively inhibited the interaction between human hepatoma HepG2 cells and the preS(21-47) ligand, suggesting that this region of the human IL-6 sequence encompasses a binding site for the HBV env protein. (c) Studies with replacement set peptides from the preS(21-47) sequence indicated that residues 21-25, 28, 31, 33-35, 39, and 43-45 can be replaced by alanine (serine) residues, while all the other residues are essential for maintaining the cell receptor/IL-6 binding activity. Further delineation of complementary sites on IL-6 and on the HBV env protein may contribute to the design of compounds inhibiting HBV replication.
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PMID:Cells transfected with human interleukin 6 cDNA acquire binding sites for the hepatitis B virus envelope protein. 133 15

Replication of hepatitis B virus (HBV) proceeds by reverse transcription of an RNA intermediate inside the viral nucleocapsid formed by the core protein. This protein contains four Cys residues which occur at equivalent positions in the core proteins of all known mammalian hepadnaviruses, suggesting that they might be of structural and/or functional importance. The four His residues of the core protein are located strikingly close to the three N-proximal cysteines. This arrangement is likewise conserved and might indicate the presence of an unconventional Cys-His box element similar to that required for nucleic acid binding in all retroviral NC proteins. In order to test the potential involvement of the core protein cysteines in virus assembly, we transiently expressed in HuH7 cells a mutant HBV genome encoding a core protein in which all cysteines are replaced by serine residues and analyzed the formation of replication-competent cores using the endogenous polymerase reaction. The mutant genome yielded products that were nearly indistinguishable from those produced by a corresponding wild-type genome, virtually ruling out the presence of a functional Cys-His box element in the hepadnaviral core protein. Density gradient analysis showed that the mutant cores were enveloped, though the efficiency of envelopment and/or the stability of the mutant enveloped particles was lowered compared to the wild-type. These data indicate that none of the steps in the viral life cycle from reverse transcription to envelopment was principally impaired. The conservedness of the cysteines might then be related to virus infectivity rather than replication; alternatively, the Cys residues might not be important for the core protein itself, but for the alternative C gene product HBeAg.
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PMID:Conserved cysteines of the hepatitis B virus core protein are not required for assembly of replication-competent core particles nor for their envelopment. 152 50

The nucleocapsid, or core particle, of hepatitis B virus is formed by 180 subunits of the core protein, which contains Cys at positions 48, 61, 107 and 183, the latter constituting the C terminus. Upon adventitious oxidation, some or all of these cysteine residues participate in the formation of disulphide bridges, leading to polymerization of the subunits within the particle. To utilize the cysteine residues as topological probes, we reduced the number of possible intersubunit crosslinks by replacing these residues individually, or in all combinations, by serine. A corresponding set of variants was constructed within the context of an assembly-competent core protein variant that lacks the highly basic C-terminal region. Analysis, by polyacrylamide gel electrophoresis under non-reducing conditions, of the oxidative crosslinking products formed by the wild-type and mutant proteins expressed in Escherichia coli, revealed a clear distinction between the three N-proximal, and the C-terminal Cys: N-proximal Cys formed intermolecular disulphide bonds only with other N-proximal cysteine residues, leading to dimerization. Cys48 and Cys61, in contrast to Cys107, could be crosslinked to the homologous cysteine residues in a second subunit, and are therefore located at the dimer interface. Cys 183 predominantly formed disulphide bonds with Cys183 in subunits other than those crosslinked by the N-proximal cysteine residues. Hence, the polymers generated by oxidation of the wild-type protein are S-S-linked dimeric N-terminal domains interconnected via Cys183/Cys183 disulphide bonds. The intermolecular crosslinks between the N-proximal cysteine residues were apparently the same in the C-terminally truncated and in the full-length proteins, corroborating the model in which the N-terminal domain and the C terminus of the HBV core protein form two distinct and structurally independent entities. The strong tendency of the N-terminal domain for dimeric interactions suggests that core protein dimers are the major intermediates in hepatitis B virus nucleocapsid assembly.
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PMID:Topological analysis of the hepatitis B virus core particle by cysteine-cysteine cross-linking. 161 86

Direct sequencing of polymerase chain reaction-amplified serum hepatitis B virus (HBV) DNA was used to characterize the precore region of HBV from Chinese patients with chronic hepatitis. Two types of mutually exclusive variants were found in hepatitis B e antigen (HBeAg)-negative patients. The first (M1) contains a substitution from proline to serine at codon 15. A second group were infected with a previously described mutant (M2) containing a translational stop codon. HBeAg-positive patients were infected with the wild-type virus or the M1-containing strain. M2 emerged in patients with wild-type infection after seroconversion to anti-HBe, whereas M1 was present during the HBeAg-positive phase. In those with fluctuating HBe status, there was no correlation between prevailing HBe serology and sequence. There was an association between infection with variants and severe chronic hepatitis. Patients infected with strains containing M1 while HBeAg positive had a worse prognosis after seroconversion to anti-HBe.
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PMID:Precore sequence variation in Chinese isolates of hepatitis B virus. 172 81

The cloning and expression of the hepatitis B middle-protein surface antigen gene in the yeast Saccharomyces cerevisiae is described. A generalized expression vector carrying the yeast glyceraldehyde-3-phosphate dehydrogenase gene promoter was used. Expressed material, in the form of supramolecular particles, was purified and characterized. Severe proteolysis within the pre-S(2) region was observed for material expressed in a wild-type yeast host. This proteolysis was substantially reduced by utilization of a protease-deficient host. Immunoblotting of sodium dodecyl sulfate-polyacrylamide gels with several antibodies of differing specificity was performed to characterize the various protein species present. All species were analyzed by N-terminal sequencing after electroelution from gels. Carbohydrate staining of gels and glycosidase treatments of the purified antigen material indicated that full-length antigen was present in both glycosylated and unglycosylated forms. Glycosylation appeared to be of both asparagine-linked and threonine/serine-linked types. Site-directed mutagenesis was used to convert two arginine residues in the pre-S(2) region of the antigen to glutamine residues. The changes abolished reactivity with one polyclonal and two monoclonal antibodies specific for epitopes within the pre-S(2) region.
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PMID:Characterization of purified hepatitis B surface antigen containing pre-S(2) epitopes expressed in Saccharomyces cerevisiae. 245 90

The molecular basis of the d or y immunological subtype of hepatitis B virus (HBV) surface antigen (HBsAg) has been investigated by mutation of specific amino acid residues. When combined with substitution of serine 113 by threonine, replacement of arginine 122 by lysine or of tyrosine 134 by phenylalanine, or both of these changes, altered the antigenic subtype of HBsAg from y+d- to y+d+. These same mutations had a more dramatic effect on the subtype of antibodies induced by the antigens, a combination of all three mutations completely changing the subtype from y to d. Our study thus identifies residues in HBsAg that not only affect the subtype but discriminate between changes in antigenic and immunogenic behaviour. It also shows how the y and d subtypes may be manifest by the same molecule.
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PMID:Mutations that change the immunological subtype of hepatitis B virus surface antigen and distinguish between antigenic and immunogenic determination. 269 11

Immunofluorescent staining of HeLa cells with rabbit antiserum raised against isolated HeLa cell nucleoli showed bright nucleolar fluorescence. Immunoprecipitation of nuclear extracts obtained from HeLa cells labelled with 35S-methionine or 32P-orthophosphate followed by gel electrophoresis of the precipitate revealed a major band of 90 kd. This antigen, called pp90, was judged to be responsible for the nucleolar fluorescence. Serine residues were predominantly phosphorylated in pp90. Similar nucleolar fluorescence was observed commonly in human cells derived from malignant tumors including acute lymphatic leukemia, adult T-cell leukemia, hepatitis B virus-associated hepatoma, adenocarcinoma, and in 5 lymphoid cells derived from Burkitt lymphoma but not in normal human lymphocytes or liver cells. In immunoprecipitation, 32P-labelled pp90 was commonly detected as the major component in all of those cells which showed nucleolar fluorescence. Resting human embryo lung (HEL) cells were negative for both nucleolar fluorescence and pp90 in immunoprecipitation, but turned positive when stimulated to grow, suggesting the involvement of pp90 in cell growth. Antigen pp90 was also induced in human lymphocytes and HEL cells by infection with Epstein-Barr virus in human cytomegalovirus, respectively, which are known to induce cell DNA synthesis in early stages of infection. A cross-reacting nucleolar antigen was detected in 2 monkey cells but not in 3 rodent cells tested.
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PMID:A human nucleolar antigen (pp90) associated with cell growth and its induction by Epstein-Barr virus and human cytomegalovirus. 609 64

The core of Dane particles, the presently accepted hepatitis B virus nucleocapsid, contains two polypeptides (P19 and P45) with the antigenicity of hepatitis B e antigen (HBeAg). The antigenicity of hepatitis B core antigen (HBcAg) was not detectable in either of them by the conventional in vitro assay methods, despite the fact that both of these polypeptides were derived from the core of Dane particles. When a rabbit had been immunized with the purified preparation of P19 emulsified in complete Freund's adjuvant, however, humoral antibody against HBcAg was produced in addition to the antibody against HBeAg. Amino acid analysis of P19 disclosed a high content of arginine (12.9%), leucine (11.9%), serine (10.3%) and proline (10.2%). The amino acid composition of P19 was found to be strikingly similar to the composition of the 183 amino acid sequence deduced from the sequence of hepatitis B virus DNA which has been presumed to be encoding HBcAg. We conclude that both HBeAg and HBcAg are antigenic determinants borne by the major polypeptide (P19) constituting the core of Dane particles.
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PMID:Demonstration of the immunogenicity of hepatitis B core antigen in a hepatitis B e antigen polypeptide (P19). 617 55

Ultrastructural studies with the transmission (TEM) and scanning (SEM) electron microscopes have added greatly to our knowledge of cellular structure and function in the liver. The normal polyhedral hepatocyte has numerous subcellular organelles, such as mitochondria, peroxisomes, lysosomes and complex rough (rer) and smooth (ser) endoplasmic reticulum. The normal hepatocyte stores glycogen, and sometimes lipid droplets, and secretes bile through the bile canaliculi between adjacent liver cells. It receives nutrients from the sinusoidal lumen across a fenestrated endothelium which is separated by the Space of Disse' from the plasma membrane. The Space of Disse' contains a scant network of reticulin fibers but no basal lamina. Two types of parasinusoidal cells are found in Disse's space: the fat storing cells of Ito, and the Pit cells which may have an endocrine function. The diseased liver has yielded much information in studies with TEM and SEM. The studies with TEM have been most helpful in studying the etiology of infectious diseases such as hepatitis B; have revealed organelle changes such as megamitochondria in cirrhosis and the fibrillar nature of alcoholic hyaline; have led to the identification of specific deposits in metabolic and storage diseases such as hemochromatosis (iron). Wilson's disease (copper), and alpha-1-antitrypsin deficiency (glycoprotein) have proven useful in identifying drug induced liver cell changes such as proliferation of SER and cholestasis, and are useful for identifying specific cell types in inflammatory and neoplastic diseases. In the future, both TEM and SEM coupled with histochemical, cytochemical, immunohistochemical and other analytic techniques will continue to add greatly to our understanding of the liver in health and disease.
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PMID:Ultrastructure of the liver and biliary tract in health and disease. 637 90

The nature of the protein kinase (PK) which phosphorylates the core protein of hepatitis B virus in vitro was studied. The PK copurified with the core particles during rate zonal centrifugation and gel chromatography. It showed the same size heterogeneity as the core particles, which consisted of a main fraction of 28-nm particles and a subfraction of 22- to 26-nm particles. DNA-containing heavy core particles with a density of 1.33 to 1.35 g/ml and less endogenous PK than did the light cores. The phosphorylation reaction had a rapid initial phase (several minutes) and a slow but long-lasting second phase (many hours). The PK had a high affinity for ATP (KM = 0.5 mumol/liter). Only few of the several hundred P21.9 subunits in one core particle were phosphorylated in vitro. The only amino acid which was phosphorylated in vitro was serine. The resistance of the introduced phospho group against alkaline phosphatase showed that the PK acceptor, and probably the enzyme itself, was located inside the core particle.
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PMID:Specificity and localization of the hepatitis B virus-associated protein kinase. 680 56


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