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)

Determination of the amino acid sequence of the immunogenic polypeptides of hepatitis B surface antigen may not only permit molecular localization of the distinct determinants a, d, and y but may also lead to the synthesis of a hapten useful in prophylactic immunization against hepatitis B virus infection. For this purpose, purified monotypic hepatitis B surface antigen of adw subtype was resolved into equal amounts of two major polypeptides (22,000 and 28,000 daltons) and up to six other minor polypeptides by polyacrylamide gel electrophoresis. With the periodate staining reaction, only the 28,000-dalton polypeptide stained as a glycoprotein. Guinea pigs immunized with the 22,000-dalton polypeptide produced potent antisera against determinants a and d, but the 28,000-dalton glycoprotein did not induce a response. Both polypeptides isolated by preparative polyacrylamide gel electrophoresis showed amino acid composition identical with that of the intact antigen. For both polypeptides, hydrazinolysis gave Ile as the carboxyterminus, and carboxypeptidase A digestion gave the same terminal sequence, Val-Tyr-Ile. Both peptides also yielded an identical sequence of amino acids in nine steps of Edman degradation--Met-Glu-Asn-Ile-Thr-Ser(Cys)-Gly-Phe-Leu. Our data suggest that hepatitis B surface antigen contains a single major immunogenic 22,000-dalton polypeptide component, part of which is modified by the addition of carbohydrate to give rise to the glycopeptide of apparent molecular weight 28,000.
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PMID:Partial amino acid sequence of two major component polypeptides of hepatitis B surface antigen. 26 93

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

Amino acid residues 101 to 180 of hepatitis B surface antigen (HBsAg) were predicted by sequencing the corresponding part of the S gene of hepatitis B virus (HBV) DNA in 46 HBsAg-positive sera, which had been subtyped by immunodiffusion with respect to d/y, w/r, w1 to w4 and q. The sequences of the nine different HBV serotypes defined by these specificities were found to be homogeneous proving that they represent consistent variations of HBV at the genomic level. Residue 127 was found to be important as were Pro, Thr and Leu for w1/w2, w3 and w4, respectively. Five residues were found to differ between ayw1 and ayw2. These were at positions 134 (Phe instead of Tyr), 143 (Thr instead of Ser), 159 (Ala instead of Gly), 161 (Tyr instead of Phe) and 168 (Val instead of Ala). However, all these residues were shared by ayw1 and adw2, implying that Arg122 was also important for w1 expression. All genomes expressing r, apart from one ayr strain, had an Ile126, which might explain the pseudo-allelism of w1 to w4 in relation to r, since this substitution might influence the w epitope. There were two regions where adw4q- and adrq- differed from all the q+ subtypes. These were located at residues 158 and 159, and at residues 177 and 178, where both the q- subtypes had amino acid substitutions in adjacent positions. The mapping of the epitopes defining these antigenic specificities will help to link information on the world-wide distribution of HBsAg subtypes to future molecular epidemiology with regard to HBV.
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PMID:Molecular basis of hepatitis B virus serotype variations within the four major subtypes. 146 53

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

Two determinants of hepatitis B surface Ag (HBsAg), identified by mAb raised against polypeptide components, were characterized immunochemically. One was expressed on HBsAg irrespective of the four major subtypes, i.e., adw, adr, ayw, and ayr, whereas the other was subtypic but not identical to any of d, y, w, and r determinants. The common determinant was generated by a synthetic pentadecapeptide with a sequence of Thr-Thr-Ser-Thr-Gly-Pro-Cys-Lys-Thr-Cys-Thr-Ile-Pro-Ala-Gln representing amino acids 115-129 of the S gene product, and detected invariably in 366 HBsAg samples in sera from asymptomatic carriers in Japan. The activity of the S gene product, as well as the peptide (115-129), to bind with the mAb was not affected by alkylation alone, but was completely lost after reductive alkylation. The antigenic activity was lost when the S gene product was severed between Lys122 and Thr123 by trypsin. A microconformation maintained by the -Cys121-Cys124 bond, therefore, would be required for the common determinant. The other mAb identified an epitope of HBsAg that was mimicked by a synthetic tetradecapeptide with a sequence of Thr-Cys-Thr-Ile-Pro-Ala-Gln-Gly-Thr-Ser-Met-Phe-Pro-Ser, representing amino acids 123-136 of the S gene product. Among 16 HBsAg samples with known S gene sequences, 5 with Ile126 possessed this subtypic determinant, but the remaining 11 with Thr126 did not. The 5 hepatitis B virus genomes encoding the subtypic determinant differed less than 5.6% from each other in the entire nucleotide sequence, but by 8.0% or more from any of the other 11 genomes without the capacity to encode it.
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PMID:Synthetic oligopeptides bearing a common or subtypic determinant of hepatitis B surface antigen. 169 80

We have constructed plasmids that express modified hepatitis B virus surface antigen (HBsAg) P31-coding genes (M-P31c, d, e, f, and i) having various genetically engineered pre-S2 regions. The plasmids contain the GAPDH (gene coding for glyceraldehyde-3-phosphate dehydrogenase) promoter and the PGK (gene coding for 3-phosphoglycerate kinase) terminator, both isolated from sake brewing yeast, Saccharomyces cerevisiae Kyokai III. Expression levels of the modified HBsAg P31 proteins in yeast are greatly increased from 0.4% to 11.7% of total cell protein. However, the specific mRNAs are expressed at equal levels and the degradation rates of the modified P31 proteins do not vary significantly. Therefore, we considered that different expression levels of the modified P31 proteins are attributed to the changes of the post-translational efficiency. And it was suggested that the conformational stability of the N-terminal peptide (Met-1-Phe-46) in the endoplasmic reticulum membrane determines the expression level of modified P31 proteins.
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PMID:Efficient expression of genetically engineered hepatitis B virus surface antigen P31 proteins in yeast. 267 25

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

The S gene encoding the major surface polypeptide of hepatitis B virus is preceded by the region pre-S(2) with a capacity to code for 55 amino acid residues. In the product of region pre-S(2), the sequence of 19 amino acid residues (amino acids 14-32 from the N terminus) representing an area of high local hydrophilicity is shared by viral strains of subtypes adr, ayw, and ayr; residue 22, phenylalanine, is replaced by leucine in a strain of the other subtype, adw. A synthetic peptide vaccine involving these 19 amino acid residues, when given to two chimpanzees, raised antibodies that bound to viral particles and protected the animals from challenge with 10(6) chimpanzee infectious doses of hepatitis B virus.
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PMID:A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees. 346 81

HLA-DR13 has been associated with resistance to two major infectious diseases of humans. To investigate the peptide binding specificity of two HLA-DR13 molecules and the effects of the Gly/Val dimorphism at position 86 of the HLA-DR beta chain on natural peptide ligands, these peptides were acid-eluted from immunoaffinity-purified HLA-DRB1*1301 and -DRB1*1302, molecules that differ only at this position. The eluted peptides were subjected to pool sequencing or individual peptide sequencing by tandem MS or Edman microsequencing. Sequences were obtained for 23 peptides from nine source proteins. Three pool sequences for each allele and the sequences of individual peptides were used to define binding motifs for each allele. Binding specificities varied only at the primary hydrophobic anchor residue, the differences being a preference for the aromatic amino acids Tyr and Phe in DRB1*1302 and a preference for Val in DRB1*1301. Synthetic analogues of the eluted peptides showed allele specificity in their binding to purified HLA-DR, and Ala-substituted peptides were used to identify the primary anchor residues for binding. The failure of some peptides eluted from DRB1*1302 (those that use aromatic amino acids as primary anchors) to bind to DRB1*1301 confirmed the different preferences for peptide anchor residues conferred by the Gly-->Val change at position 86. These data suggest a molecular basis for the differential associations of HLA-DRB1*1301 and DRB1*1302 with resistance to severe malaria and clearance of hepatitis B virus infection.
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PMID:Naturally processed peptides from two disease-resistance-associated HLA-DR13 alleles show related sequence motifs and the effects of the dimorphism at position 86 of the HLA-DR beta chain. 760 34

Termination mutations in the precore open reading frame of hepatitis B virus (HBV) variants with defective hepatitis B e antigen (HBeAg) production have been demonstrated in both infected patients who have seroconverted to anti-HBe and those with fulminant hepatitis B. A donated plasma sample was found to be positive for the hepatitis B surface antigen, but negative for both HBeAg and anti-HBe. The HBV DNA titer in the plasma was estimated to be 32 pg/ml, and circulating virus-like particles were observed by electron microscopy. The entire nucleotide sequence of the virus was determined and at least 7 nucleotides were found to be unique when compared with previously reported sequences. These nucleotides created no termination codon in the precore/core, pol, preS/S and HBx open reading frames. The deduced amino acid substitutions were 28 Arg--Gln, 94 His--Tyr, 131 Val--Ile and 132 Phe--Tyr of HBx and 715 Met--Val and 789 Asp--Asn of pol. Furthermore, the precore and core/pregenome promoter contained altered 1764 A, 1766 T and 1768 A. Therefore, mutations in regions other than the precore open reading frame can cause defective HBeAg production.
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PMID:Mutations in the transcriptional regulatory region of the precore and core/pregenome of a hepatitis B virus with defective HBeAg production. 785 32


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