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)

Human hepatitis B virus core protein expressed in E. coli assembles into two sizes of particle. We have determined their three-dimensional structures by electron cryomicroscopy and image processing. The large and small particles correspond to triangulation number T = 4 and T = 3 dimer clustered packings, containing 240 and 180 protein subunits, respectively. The local packing of subunits is very similar in the two sizes of particle and shows holes or channels through the shell. The native viral core particle packages RNA and is active in reverse transcription to DNA. The holes we observe may provide access for the necessary small molecules. Shells assembled from the intact core protein contain additional material, probably RNA, which appears as an icosahedrally ordered inner shell in the three-dimensional map.
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PMID:Three-dimensional structure of hepatitis B virus core particles determined by electron cryomicroscopy. 800 80

Hepatitis B virus (HBV) core antigen (HBcAg) particles purified from Escherichia coli were probed in a competition enzyme immunoassay (EIA) with a panel of 16 murine monoclonal antibodies (MAbs) directed to different forms of core protein. The linear binding sites of the MAbs were mapped by combination of solid-phase and competition EIA using synthetic peptides covering the complete sequence of HBV core protein. Relative accessibilities of the linear binding sites at the HBcAg surface were investigated by comparing reactivities in solution of the MAbs to (i) two genetic variants of particulate HBcAg, (ii) denatured core protein, and (iii) synthetic peptides mimicking the appropriate linear binding sites. Further, accessibilities of HBV preS1 and preS2 epitopes (introduced into core protein at positions 77 or 144) at the surface of chimeric HBcAg particles were investigated. The previously described surface localization of core protein region 78-83 at the core particle surface was confirmed. In addition, another region, encompassing residues 127-133, was found to occupy a surface position at particulate HBcAg, whereas regions 9-20 and 133-145 were exposed after denaturation of the core protein and at synthetic peptides but not at particulate HBcAg.
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PMID:Identification of hepatitis B virus core protein regions exposed or internalized at the surface of HBcAg particles by scanning with monoclonal antibodies. 803 Feb 52

Transgenic mice that express the hepatitis B virus core protein were used to examine factors that influence the intracellular localization of nucleocapsid particles in the primary hepatocyte in vivo. In this model, viral nucleocapsid particles are strictly localized to the nucleus of the hepatocyte except when the nuclear membrane dissolves during cell division, at which time they enter the cytoplasm. The cytoplasmic nucleocapsid particles do not reenter the nucleus, however, when the nuclear membrane re-forms after cell division. The data support the notion that nucleocapsid particles can form de novo within the nucleus, and they suggest that performed nucleocapsid particles cannot be transported across the intact nuclear membrane in either direction. The results imply that nucleocapsid disassembly is probably required for entry of the hepadnaviral genome into the nucleus, and they question the role of the intranuclear viral nucleocapsid particle during the viral life cycle.
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PMID:Hepatitis B virus nucleocapsid particles do not cross the hepatocyte nuclear membrane in transgenic mice. 805 29

By performing immunofluorescence staining assays in confluent COS-7 cells, hepatitis B virus core, small surface and large surface proteins were found to localize largely in the nucleus, diffusely in the cytoplasm, and accumulatively in a perinuclear area, respectively. When two proteins were co-expressed, the core protein was found co-localized with the large but not small surface protein in the cytoplasm. By performing subcellular fractionation experiments, the large surface protein was found to reduce the amount of the core protein in the nuclear fraction to an undetectable level. These results indicate that the large but not small surface protein can alter the subcellular localization of the core protein.
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PMID:Alteration of the subcellular localization of hepatitis B virus core protein by large but not small surface proteins. 809 50

As part of the Gambia Hepatitis Intervention Study, hepatitis B antigens and antibodies were assayed in 720 3-4 year old children who had received 4 doses of 10 mcg plasma-derived hepatitis B vaccine in infancy, the findings were compared with 816 controls. The cross sectional study took place from September, 1990, to July, 1991. Study subjects were tested for hepatitis B core antigen (HBcAg), as well as antigens and antibodies to hepatitis surface, e, and core protein, and those testing positive were tested a year later for HBsAg to determine chronic carrier status. Children negative for core antibody and surface antigen were considered uninfected; those positive for core antibody were considered infected; those positive for surface antigen 2 times 6 months apart were considered carriers. 4.6% of the vaccinated children were infected, and 0.6% were chronic carriers. 3 of these carriers had infected or carrier mothers, and 1 had only received 1 dose of vaccine. In the controls, there were 29% judged infected by anti-HBc, including 13% who were also positive for HBsAg. 86% of these were considered chronic carriers when tested a year later. Thus the vaccine was estimated to be 84% effective against infection and 94% effective against chronic carriage. The current Gambian vaccine consists of 2.5 mcg recombinant hepatitis B vaccine.
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PMID:Efficacy of hepatitis B vaccine in the Gambian expanded programme on immunisation. 809 13

The roles of different regions of the duck hepatitis B virus (DHBV) core protein on viral capsid assembly and related functions were examined. Twelve deletion and insertion mutations which covered 80% of the DHBV C open reading frame were constructed and expressed in Escherichia coli. The N-terminal region (amino acids 3 to 66) of DHBV core protein was important for its tertiary structure and function in E. coli. The expressed core mutants without this region apparently inhibited E. coli growth. The results of transmission electron microscopy of E. coli thin sections, capsid agarose gel, and sucrose gradient sedimentation demonstrated that a few DHBV core mutants with insertion in the N terminus and deletion in the C terminus retained the ability to form core-like particles in E. coli. However, other mutations in most of N-terminal and central regions strongly inhibited the self-assembly ability of DHBV core protein in E. coli. In addition, the mutant with a C-terminal region deletion (amino acids 181 to 228) lost most of the nucleic acid-binding activity of the DHBV core protein.
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PMID:Capsid assembly and involved function analysis of twelve core protein mutants of duck hepatitis B virus. 825 45

To analyse the immunological mechanism of hepatocellular injury in hepatitis B virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia virus (RVV) expressing surface protein (S), precore/core protein (PC), and core protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their spleen cells were then harvested and stimulated in vitro with the histocompatible transfectant, which stably expressed hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as effectors. As the targets, L cells (H-2k) infected with individual RVV were used. Cytotoxic test was performed with various combinations and ratios of effectors and targets. The reactivity of PC-primed effectors against PC-expressing targets was greatest with 71.4% specific lysis on average at an effector/target ratio of 12.5:1 among all the combinations. C-primed effectors against C-expressing target also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of 12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity to the targets expressing other nucleocapsid antigen, respectively. S-primed effectors showed less lytic activity against S-expressing targets (specific lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti-CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not by anti-CD4 or anti-MHC class II. These findings suggest that endogenously synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC class I-restricted CTL in H-2k mice and that this system may work as an efficient model to study immunopathogenesis of HBV infection.
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PMID:Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T-cell response. 826 60

The hepatitis B virus (HBV) core protein has been found in the nucleus, the cytoplasm, or both of HBV-infected hepatocytes. However, the mechanism that regulates the subcellular localization of the HBV core protein is still unclear. In this report, we demonstrate that nuclear localization of the HBV core protein is cell cycle-regulated in two different cell lines. The amount of the core protein in the nucleus was increased during the G1 phase, reduced to an undetectable level during the S phase, and increased again when the cells were confluent and ceased to grow. Thus, the nuclear localization of the core protein during HBV infection can be at least partially attributed to liver injury and regeneration, which cause the hepatocytes to enter cell cycles. Based on the observation that the cytoplasmic core protein was phosphorylated and the nuclear core protein was not, we speculate that nuclear localization of the HBV core protein is negatively regulated by phosphorylation during the cell cycle.
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PMID:Cell cycle regulation of nuclear localization of hepatitis B virus core protein. 834 55

Hepatitis B and C viruses (HBV and HCV, respectively) are associated with acute and chronic liver diseases and hepatocellular carcinoma. To elucidate the molecular status of superinfection with these two hepatitis viruses, we cotransfected the full-length or truncated version of HCV structural genes (core and envelope 1) together with the cloned HBV DNA into a human hepatoma cell line (HuH-7). Expression of HBV-specific major transcripts (3.5 and 2.1 kb), as well as HBV antigens (hepatitis B surface antigen and hepatitis B e and core antigens), was reduced about two- to fourfold by the presence of the HCV structural genes. In addition, the secretion of HBV viral particles, including the viral nucleocapsid and mature virion, was drastically suppressed about 20-fold. Analysis of the intracellular HBV core protein-associated nucleic acid indicated that the encapsidated HBV pregenomic RNA was similarly reduced about 14-fold. Deletion analysis of the HCV structural genes demonstrated that the core gene alone or the fragment containing the core protein's N-terminal 122 amino acid residues conferred the same level of suppressive activity as the full-length structural genes. By indirect immunofluorescence, we found that the core protein of HCV was located in the cytoplasm of transfected HuH-7 cells at day 3 posttransfection and was targeted to the nucleus at day 6. Thus, the kinetics of the suppressive effect exerted by HCV constructs matched the timing of core protein entrance into the nucleus. Our results substantiate the clinical finding that HBV markers are suppressed by superinfection with HCV and further imply that this inhibitory effect may occur in the processes of transcription and encapsidation of HBV pregenomic RNA and may be mediated by the core protein of HCV. The deduced amino acid sequence of the HCV core protein has revealed that it is a basic protein which contains a putative DNA-binding motif (SPRG), as well as triplicate nuclear localization signals and several putative protein kinase A and C recognition sites. These characteristics imply that the HCV core protein can also function as a gene-regulatory protein.
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PMID:Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. 839 58

Either parts or multiple copies of the core gene of hepatitis C virus (HCV) were fused to the 3' terminus of the hepatitis B virus (HBV) core gene with 34 codons removed. As many as four copies of HCV core protein (720 amino acids) were fused to the carboxy terminus of truncated HBV core protein (149 amino acids) without preventing the assembly of HBV core particles. Chimeric core particles were sandwiched between monoclonal antibody to HBV core and that to HCV core, thereby indicating that antigenic determinants of both HBV and HCV cores were accessible on them. Proteolytic digestion deprived chimeric core particles of the antigenicity for the HCV core without affecting that of the HBV core, confirming the surface exposure of HCV core determinants. The density of HCV core determinants on chimeric core particles increased as copies of fused HCV core protein were increased. Hybrid core particles with multiple HCV core determinants would be instrumental as an antigen probe for detecting class-specific antibodies to the HCV core in patients with acute and chronic hepatitis C and for simultaneous detection of antibodies to HBV core and those to HCV core in donated blood.
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PMID:Chimeric hepatitis B virus core particles with parts or copies of the hepatitis C virus core protein. 839 69


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