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)

The minimal amino acid sequence sufficient to be recognized efficiently by virus-attachment inhibiting murine monoclonal anti-preS1 antibody MA18/7 has been determined. We have constructed a recombinant gene library using the cloned coat protein gene of Escherichia coli RNA bacteriophage fr as a carrier. Different fragments of preS1 region from cloned hepatitis B virus (HBV) genomes, subtype ayw and adw, were inserted at position 2 of the 129 amino acid-long fr coat protein gene in the appropriate E. coli expression vectors. Fine mapping of preS1 epitope recognized by MA18/7 was accomplished by bidirectional shortening of the preS1 within original recombinant preS-fr coat protein genes with Bal31 exonuclease. Immunoblot analysis of the obtained recombinant protein library revealed that the tetrapeptide Asp-Pro-Ala-Phe (DPAF), located at the position preS(31-34) and conserved in all known HBV genomes, is sufficient to bind MA18/7 antibody. Recognition of the preS1 region by MA18/7 occurred irrespective of the amino acid context surrounding this DPAF tetrapeptide. Further shortening of this minimal epitope from the left or from the right side completely prevented antibody binding in immunoblots.
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PMID:Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes. 127 69

Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transpositional events that include both viral and nonviral genetic entities. Although it is probable that some RT-bearing genetic elements like the different types of AIDS viruses and the mammalian LINE family have arisen in recent geological times, the possibility that reverse transcription first took place in the early Archean is supported by (1) the hypothesis that RNA preceded DNA as cellular genetic material; (2) the existence of homologous regions of the subunit tau of the E. coli DNA polymerase III with the simian immunodeficiency virus RT, the hepatitis B virus RT, and the beta' subunit of the E. coli RNA polymerase (McHenry et al. 1988); (3) the presence of several conserved motifs, including a 14-amino-acid segment that consists of an Asp-Asp pair flanked by hydrophobic amino acids, which are found in all RTs and in most cellular and viral RNA polymerases. However, whether extant RTs descend from the primitive polymerase involved in the RNA-to-DNA transition remains unproven. Substrate specificity of the AMV and HIV-1 RTs can be modified in the presence of Mn2+, a cation which allows them to add ribonucleotides to an oligo (dG) primer in a template-dependent reaction. This change in specificity is comparable to that observed under similar conditions in other nucleic acid polymerases. This experimentally induced change in RT substrate specificity may explain previous observations on the misincorporation of ribonucleotides by the Maloney murine sarcoma virus RT in the minus and plus DNA of this retrovirus (Chen and Temin 1980). Our results also suggest that HIV-infected macrophages and T-cell cells may contain mixed polynucleotides containing both ribo- and deoxyribonucleotides. The evolutionary significance of these changes in substrate specificities of nucleic acid polymerases is also discussed.
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PMID:On the early emergence of reverse transcription: theoretical basis and experimental evidence. 128 61

A hepatitis B virus preS2 deletion library with the preS2 sequence fused to the coat protein of the RNA phage fr (fr CP) as a carrier has been constructed and used for the approximate localization of epitope recognized by a panel of murine monoclonal anti-preS2 antibodies. DNA copies of putative preS2 epitopes were synthesized and cloned within the fr CP gene. Tetrapeptide Gln-Asp-Pro-Arg (QDPR) corresponding to the preS (132-135) sequence was found to be the minimal sufficient recognition site for one of the monoclonal antibodies, S26. The closely related tetrapeptide EDPR did not mimic the epitope activity of QDPR.
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PMID:Tetrapeptide QDPR is a minimal immunodominant epitope within the preS2 domain of hepatitis B virus. 144 23

The molecular basis of the biophysical and antigenic differences between the cellular core protein (HBc protein) and the secreted core protein (HBe protein) of human hepatitis B virus was examined. The data show that the properties which distinguish the HBe protein from the HBc protein are due mostly to the 10-amino-acid portion of the HBe leader sequence which remains attached to the HBe protein after cleavage. A cysteine located within this region determines the quaternary structure and the antigenicity of the HBe protein. If this cysteine is lacking, the HBe protein, which is predominantly a monomer with only HBe antigenicity, is expressed as a disulfide-linked homodimer showing both HBe and HBc antigenicity. However, dimerization of the HBe protein was found to be neither sufficient nor required for particle formation. In fact, aggregation of the HBe protein was found to be inhibited by the strongly hydrophobic tripeptide Trp-Leu-Trp, which is also located in the noncleaved portion of the signal sequence. If this tripeptide was converted into either Asp-Asn-Asn or Ala-Asp-Leu, the HBe protein assembled into particles, independent of the presence of the cysteine.
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PMID:A cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B virus. 150 Dec 77

The X protein of hepatitis B virus (HBV) consists of 154 amino acids and trans-activates various cellular and viral promoters and enhancers. To investigate the essential amino acid sequences of X protein for trans-activation function, various mutations were introduced into the X open reading frame and analysed for trans-activation activity by chloramphenicol acetyltransferase assay. The amino acid sequences 46-52 (especially Pro-46, His-49 and His-52), 61-69 (especially Cys-61, Gly-67 to Pro-68 and Cys-69) and 132-139 (especially Phe-132, Cys-137 and His-139) of HBV X protein were found to be essential for the trans-activation function. These three sequences are included in the conserved amino acid sequences among hepadna virus X proteins. The first one could form a domain-like structure characteristic of histidine/aspartic acid requirement. The second and the third are homologous to the Kunitz domain of Kunitz-type serine protease inhibitors. The amino acids 5-27 region was found to make no positive contribution to the trans-activation function like the last 12 amino acids in the carboxy-terminal region [Takada, S. & Koike, K. (1990). Proc. Natl. Acad. Sci. USA, 87, 5628-5632]. From these findings, the trans-activation function of X protein appears to be dependent on at least two types of domain-like structures.
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PMID:Identification of three essential regions of hepatitis B virus X protein for trans-activation function. 154 57

Four hundred and four patients (273 men, 131 women) aged 3 to 85 years with chronic Hepatitis B virus (HBV) infection seen during a five year period were analysed. At presentation, 177 patients (44%) were Hepatitis B e Antigen (HBeAg) positive (mean age 32 years) and 217 patients (54%) were anti-HBe-positive (mean age 40 years). Ten patients (2%) were negative for HBeAg and anti-HBe. Serum HBV-DNA was detected in 169 patients (42%). 85% of the HBeAg-positive patients had detectable serum HBV-DNA and 9% of the HBeAg-negative patients were positive for serum HBV-DNA. The mean serum Alanine amino-transferase (ALT) and Aspartate amino-transferase (AST) levels were higher in HBeAg-positive patients (75 and 52 iu/l) than in HBeAg negative patients (46 and 37 iu/l) (P less than 0.001). Liver biopsies were performed in 135 patients. Fifty-three (39%) had minimal changes, 61 (45%) chronic hepatitis (CPH, CLH & CAH) and 21 (16%) cirrhosis. There was no significant difference in the histologic distribution between HBeAg-positive and HBeAg-negative groups. Two hundred and fifty eight patients were followed up for a mean duration of 2 years (range 3 to 108 months). The cumulative probability of clearing HBeAg at the end of the first, second and third year were 14%, 16% and 18% respectively. Of these, the cumulative probability of developing anti-HBe over one, two and three years were 8%, 9% and 11% respectively. Reversion to HBeAg occurred in 1.5% of patients who were HBeAg-negative at presentation and 11% of HBeAg-positive patients who cleared HBeAg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic hepatitis B infection in Singapore. 179 64

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.
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PMID:The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. 246 92

The hepatitis B virus (HBV) C gene directs the synthesis of two major gene products: HBV core antigen (HBcAg[p21c]), which forms the nucleocapsid, and HBV e antigen (HBeAg [p17e]), a secreted antigen that is produced by several processing events during its maturation. These proteins contain an amino acid sequence similar to the active-site residues of aspartic acid and retroviral proteases. On the basis of this sequence similarity, which is highly conserved among mammalian hepadnaviruses, a model has been put forward according to which processing to HBeAg is due to self-cleavage of p21c involving the proteaselike sequence. Using site-directed mutagenesis in conjunction with transient expression of HBV proteins in the human hepatoma cell line HepG2, we tested this hypothesis. Our results with HBV mutants in which one or two of the conserved amino acids have been replaced by others suggest strongly that processing to HBeAg does not depend on the presence of an intact proteaselike sequence in the core protein. Attempts to detect an influence of this sequence on the processing of HBV P gene products into enzymatically active viral polymerase also gave no conclusive evidence for the existence of an HBV protease. Mutations replacing the putatively essential aspartic acid showed little effect on polymerase activity. Additional substitution of the likewise conserved threonine residue by alanine, in contrast, almost abolished the activity of the polymerase. We conclude that an HBV protease, if it exists, is functionally different from aspartic acid and retroviral proteases.
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PMID:Proteaselike sequence in hepatitis B virus core antigen is not required for e antigen generation and may not be part of an aspartic acid-type protease. 265 1

The C gene products of all mammalian hepadnaviruses contain a region with sequence similarities to the catalytic center of the aspartyl proteases. This region could have the capacity to cleave precore proteins, leading to the synthesis of e antigen. By site-directed mutagenesis on a plasmid containing the hepatitis B virus C gene, we have replaced either the Asp residue of the putative aspartyl protease catalytic center or an Asp residue located 3 amino acids upstream. Transient expression of the mutated hepatitis B virus C gene in human and mouse cells showed that none of these mutations prevented the secretion of an accurately processed HBe antigen. Thus, we demonstrated that the aspartyl protease responsible for e antigen precursor processing is not C gene encoded but is more likely to be a cellular enzyme. From these results, we suggest a model for the mechanism of e antigen synthesis.
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PMID:Biosynthesis of hepatitis B virus e antigen: directed mutagenesis of the putative aspartyl protease site. 268 58

The effect on hepatitis B surface antigen (HBsAg) of reagents considered specific for each of the amino acid residues, lysine, methionine, cysteine, arginine, tyrosine, tryptophan, and glutamic (aspartic) acid, was studied. Based on the observed alterations of HBsAg antigenicity and the known amino acid sequence of the HBsAg polypeptide, a major antigenic determinant was localized within the sequence: Pro-Ser-Cys-Cys-Cys-Thr-Lys-Pro-Thr(Ser)-Asp-Gly-Asn-Cys-Thr-Cys-Ile-Pro-Ile-Pr o-Ser-Ser, corresponding to residues 135-155. The asparagine-linked saccharide chains are not essential for HBsAg antigenicity.
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PMID:Localization of a hepatitis B surface antigen determinant deduced from results of chemical modifications. 616 48


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