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)

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.
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PMID:Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma. 132 6

A chimeric protein containing most of the hepatitis B virus preS2 region (amino acid residues 1-48) upstream to, and colinear with the amino-terminus of bluetongue virus VP7 protein (preS2-VP7) was expressed by a recombinant Autographa californica nuclear polyhedrosis virus (AcNPV). The chimeric protein formed BTV core-like particles (CLPs) in Spodoptera frugiperda cells only when the cells were coinfected with this recombinant virus and a recombinant baculovirus that expresses unmodified VP7 and VP3 of BTV. The ratio of preS2-VP7 incorporated into CLPs was influenced by the relative multiplicities of infection of the two viruses. Immunoelectron microscopy of the chimeric particles indicated that the preS2 epitope was exposed on the surface of the CLPs. When insect cells were coinfected with the preS2-VP7 recombinant virus and a baculovirus vector that synthesized only the VP3 protein, no CLPs were identified.
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PMID:Presentation of hepatitis B virus preS2 epitope on bluetongue virus core-like particles. 138 38

The regulatory immediate-early (IE) protein pp89 of murine cytomegalovirus induces CD8+ T lymphocytes that protect against lethal murine cytomegalovirus infection. The IE1 epitope is the only epitope of pp89 that is recognized by BALB/c cytolytic T lymphocytes (CTL). Using synthetic peptides, the optimal and minimal antigenic sequences of the IE1 epitope have been defined. To evaluate the predictive value of data obtained with synthetic peptides, recombinant vaccines encoding this single T-cell epitope were constructed using as a vector the hepatitis B virus core antigen encoded in recombinant vaccinia virus. In infected cells expressing the chimeric proteins, only IE1 epitope sequences that were recognized as synthetic peptides at concentrations lower than 10(-6) M were presented to CTL. Vaccination of mice with the recombinant vaccinia virus that encoded a chimeric protein carrying the optimal 9-amino-acid IE1 epitope sequence elicited CD8+ T lymphocytes with antiviral activity and, furthermore, protected against lethal disease. The results thus show for the first time that recombinant vaccines containing a single foreign nonameric CTL epitope can induce T-lymphocyte-mediated protective immunity.
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PMID:Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. 171 Feb 86

Hepatitis B virus (HBV) particles are generated by budding of preformed cytoplasmic nucleocapsids into endoplasmic reticulum (ER) membranes containing the three viral envelope proteins (L, M, and S). We have examined the contributions of the envelope proteins to virion assembly by using cultured hepatoma cells transfected with mutant HBV genomes bearing lesions in the envelope coding regions. We show here that HBV nucleocapsids are not released from cells without expression of envelope proteins, implying an active role for these proteins in viral morphogenesis. S and L but not M proteins are necessary for virion production. L protein over-expression inhibits virion release, just as it inhibits the release of subviral hepatitis B surface antigen (HBsAg) particles. Mutant L proteins that are no longer capable of retaining HBsAg particles in the ER still allow virion formation, indicating that this ER retention reaction is not required for viral budding. Myristoylation of L protein is also dispensable for virion formation. A chimeric protein bearing foreign epitopes fused to the S protein can be incorporated into virions when coexpressed with the wild-type envelope proteins. Models for the dependence of virion formation on both L and S proteins are discussed.
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PMID:The role of envelope proteins in hepatitis B virus assembly. 199 57

With the use of chemical-enzymatic synthesis, a polynucleotide (I) has been obtained which codes the amino acid sequence 93-109 of the hepatitis B surface antigen (HBsAg). The plasmid pHS12, constructed by insertion of (I) into pBR325 between EcoRI and BamHI sites, transformed E. coli HB101 cells. The plasmid expression in cell-free system produced a chimeric protein, its molecular weight corresponding to that a polypeptide containing the heptadecapeptide from HBsAg. An approach is discussed for creating a new type of vaccines on the basis of chimeric proteins containing the antigenic determinants of virus proteins.
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PMID:[Synthesis and expression of the DNA fragment coding the antigenic determinant of the surface antigen protein of hepatitis B virus]. 620 38

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at high levels in Escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. These fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and FMDV-neutralizing antibodies in guinea pigs. The chimeric particles bound specifically to cultured eukaryotic cells. Mutant particles carrying the tripeptide sequence RGE in place of RGD and the use of a competitive peptide, GRGDS, confirmed the critical involvement of the RGD sequence in this binding. The chimeric particles also bound to purified integrins, and inhibition by chain-specific anti-integrin monoclonal antibodies implicated alpha 5 beta 1 as a candidate cell receptor for both the chimeric particle and FMDV. Some serotypes of FMDV bound to beta 1 integrins in solid- phase assays, and the chimeric particles competed with FMDV for binding to susceptible eukaryotic cells. Thus, HBc particles may provide a simple, general system for exploring the interactions of specific peptide sequences with cellular receptors.
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PMID:Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions. 864 42

The hepatitis B virus (HBV) nucleocapsid consists of 240 viral core proteins that are arranged in a highly symmetrical structure, HBV replication can only take place inside intact nucleocapsids. In the present study, we investigated whether genetically engineered core mutants can inhibit viral replication by interfering with the formation of intact nucleocapsids. Using the duck hepatitis B virus (DHBV) model, a series of core protein mutants was generated. Polymerase chain reaction-amplified fragments from the bacterial lacZ gene expressing up to 282 amino acids were added either to the amino- or carboxy-terminus of the DHBV core protein. In addition, carboxy-terminal extensions were generated by fusing the DHBV core protein with the DHBV small surface protein or various fragments of the viral polymerase. Finally, the green fluorescent protein (GFP) was fused in-frame to the carboxy-terminus of the DHBV core protein. In this chimeric protein, GFP is still functional and can act as a reporter molecule. The various core protein mutants were tested for their potential antiviral activity by cotransfection with a replication-competent DHBV construct into the avian hepatoma cell line LMH. Carboxy-terminal, but not amino-terminal, DHBV core mutants inhibited DHBV replication by up to 90% at an effector-to-target ratio of 1:10, thus displaying a dominant negative phenotype. Antiviral activity was species-specific and caused by posttranslational interference with viral replication. The DHBV core-GFP fusion protein should be an ideal tool to assess the antiviral potential of dominant negative core proteins in vivo.
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PMID:Inhibition of viral replication by genetically engineered mutants of the duck hepatitis B virus core protein. 869 Mar 95

The X gene product of the human hepatitis B virus (HBx) is a transcriptional activator of various viral and cellular genes. We recently have determined that the production of tumor necrosis factor-alpha (TNF-alpha) by HBV-infected hepatocytes is transcriptionally up-regulated by HBx, involving nuclear factor of activated T cells (NF-AT)-dependent activation of the TNF-alpha gene promoter. Here we show that HBx activates NF-AT by a cyclosporin A-sensitive mechanism involving dephosphorylation and nuclear translocation of the transcription factor. Luciferase gene expression assays demonstrated that HBx transactivates transcription through NF-AT-binding sites and activates a Gal4-NF-AT chimeric protein. DNA-protein interaction assays revealed that HBx induces the formation of NF-AT-containing DNA-binding complexes. Immunofluorescence analysis demonstrated that HBx induces the nuclear translocation of NF-AT, which can be blocked by the immunosuppressive drug cyclosporin A. Furthermore, immunoblot analysis showed that the HBx-induced activation and translocation of NF-AT are associated with its dephosphorylation. Thus, HBx may play a relevant role in the intrahepatic inflammatory processes by inducing locally the expression of cytokines that are regulated by NF-AT.
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PMID:The hepatitis B virus X protein activates nuclear factor of activated T cells (NF-AT) by a cyclosporin A-sensitive pathway. 984 11

The nucleocapsid of hepatitis B virus (HBV), or HBcAg, is a highly symmetric structure formed by multiple dimers of a single core protein that contains potent T helper epitopes in its 183-aa sequence. Both factors make HBcAg an unusually strong immunogen and an attractive candidate as a carrier for foreign epitopes. The immunodominant c/e1 epitope on the capsid has been suggested as a superior location to convey high immunogenicity to a heterologous sequence. Because of its central position, however, any c/e1 insert disrupts the core protein's primary sequence; hence, only peptides, or rather small protein fragments seemed to be compatible with particle formation. According to recent structural data, the epitope is located at the tips of prominent surface spikes formed by the very stable dimer interfaces. We therefore reasoned that much larger inserts might be tolerated, provided the individual parts of a corresponding fusion protein could fold independently. Using the green fluorescent protein (GFP) as a model insert, we show that the chimeric protein efficiently forms fluorescent particles; hence, all of its structurally important parts must be properly folded. We also demonstrate that the GFP domains are surface-exposed and that the chimeric particles elicit a potent humoral response against native GFP. Hence, proteins of at least up to 238 aa can be natively displayed on the surface of HBV core particles. Such chimeras may not only be useful as vaccines but may also open the way for high resolution structural analyses of nonassembling proteins by electron microscopy.
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PMID:Native display of complete foreign protein domains on the surface of hepatitis B virus capsids. 1005 69

The currently marketed hepatitis B vaccines in the U.S. are based on the recombinant major hepatitis B surface antigen (HBsAg) of hepatitis B virus. Although a large majority of individuals develop protective immunity to HBV-induced disease after three immunizations, routinely a small but a significant percentage of the human population does not respond well to these vaccines. In this report, we describe the generation of a novel HBsAg molecule containing a Th epitope derived from tetanus toxoid (TT). Using recombinant DNA technology. the TT Th epitope (TTe) was inserted into the HBsAg coding sequence. Using a recombinant adenovirus expression system, HBsAg TTe chimeric protein was produced in A549 cells and found to be secreted into culture medium as 22 nm particles. The chimeric HBsAg particles were readily purified by immunoaffinity chromatography and their immunogenicity was evaluated relative to native HBsAg produced in an adenovirus expression system. When evaluated in inbred and outbred strains of mice, HBsAg TTe was shown to enhance several-fold the anti-HBs response relative to native HBsAg. Further enhanced responses were observed in mice primed with TT. This highly immunogenic form of HBsAg has promise as an improved HBsAg subunit vaccine.
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PMID:Enhanced immunogenicity of hepatitis B surface antigen by insertion of a helper T cell epitope from tetanus toxoid. 1019 12


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