Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An oligonucleotide complementary to a leader RNA of positive-stranded mouse hepatitis virus (MHV) was tested for the effect on the viral multiplication in mouse DBT cells. A 14-mer antisense oligonucleotide contained a sequence complementary to the conserved pentanucleotide sequence, UCUAA, of the leader RNA. A treatment of MHV-infected cells with the antisense oligonucleotide at concentrations from 5 to 25 microM had an inhibitory effect on the viral multiplication and reduced the synthesis of viral specific mRNA and proteins. No inhibitory effect was observed when the cells were treated with sense oligonucleotide and oligonucleotide which contained unrelated sequences at concentrations from 1 to 10 microM. These results showed that antisense oligonucleotide against the leader RNA reduced the multiplication of positive-stranded RNA virus, MHV.
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PMID:Inhibition of mouse hepatitis virus multiplication by an oligonucleotide complementary to the leader RNA. 132 13

Immunoassays were developed to detect antibodies against oligopeptides deduced from the putative core gene of hepatitis C virus, and their performances were compared with that of the commercial immunoassay for antibodies against the product of nonstructural regions of hepatitis C virus (anti-C100-3). A 19-mer oligopeptide (CP10) and a 36-mer oligopeptide (CP9) were chemically synthesized, which represented hydrophilic regions of the product of the hepatitis C virus core gene. They were used to capture corresponding antibodies, anti-CP10 and anti-CP9, by enzyme-linked immunosorbent assay in sera from patients with acute or chronic non-A, non-B liver disease and in blood donations. At the onset of acute non-A, non-B hepatitis, anti-CP10 was detected in 15 of 20 patients (75%), and anti-CP9 was detected in 14 patients (70%). This was more frequent than anti-C100-3, which was found in only 9 patients (45%). In 186 patients with chronic non-A, non-B liver disease, anti-CP9, anti-CP10 or both were detected in 170 patients (91%). This was more frequent than anti-C100-3, which was found in 138 patients (74%). Blood with anti-CP10 as the single serological marker for hepatitis C virus infection transmitted non-A, non-B hepatitis by needlestick exposure. In sera from 558 apparently healthy blood donors, anti-CP10 was detected in 55 donors (9.9%), anti-CP9 was detected in 26 donors (4.7%) and anti-C100-3 was detected in 7 donors (1.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antibodies against synthetic oligopeptides deduced from the putative core gene for the diagnosis of hepatitis virus infection. 131 Apr 78

An enzyme-linked immunosorbent assay was developed for the determination of antibodies against the putative capsid protein of hepatitis C virus (HCV). A 36-mer oligopeptide with a sequence of RRGPRLGVRATRKTSERSQPRGRRQPIPKVRRPEGR (CP9) was synthesized; it was selected on the translation product of the presumptive HCV core gene, because of a high local hydrophilicity and excellent conservation by different HCV strains. The synthetic peptide was immobilized on a solid-support to capture antibodies directed to CP9 (anti-CP9) in test sera, which were detected by Fab' fragments of monoclonal anti-human IgG/gamma labeled with horseradish peroxidase. The specificity of anti-CP9 was confirmed by absorption tests. Anti-CP9 was detected in 13 (68%) of 19 patients with sporadic acute non-A, non-B (NANB) hepatitis and in 15 (83%) of 18 patients with post-transfusion acute NANB hepatitis. In 7 cases of acute NANB hepatitis who were followed, anti-CP9 developed earlier than antibodies against HCV (anti-HCV) detectable by a commercial assay kit. Among patients with chronic NANB liver diseases, anti-CP9 was detected in 103 (77%) of 133 with chronic hepatitis, 70 (62%) of 113 with liver cirrhosis and 31 (76%) of 41 with hepatocellular carcinoma. Anti-CP9 and anti-HCV overlapped in 175 (54%) among 324 cases of acute or chronic NANB liver diseases; 58 (18%) were positive only for anti-CP9 while 49 (15%) were positive only for anti-HCV. HCV RNA was detected, by amplifying HCV cDNA with polymerase chain reaction, in 10 of 11 sera positive only for anti-CP9. Among sera from 606 blood donors, 21 were positive only for anti-CP9. HCV RNA was detected in 5 (24%) of them, all of which had A492 values greater than 0.600 in ELISA for anti-CP9. Based on these results, anti-CP9 would complement anti-HCV for the diagnosis of HCV infection and contribute toward further decreasing posttransfusion NANB hepatitis.
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PMID:Enzyme-linked immunosorbent assay for antibodies against the capsid protein of hepatitis C virus with a synthetic oligopeptide. 196 54

To identify conserved humoral antigenic determinants within the hepatitis C virus (HCV) envelope protein E2, we expressed a peptide library containing random short fragments of the HCV envelope in yeast. Clones were identified using a monospecific rabbit antibody to a region downstream of the E2 hypervariable region. The clones define the limits of two original antigenic domains: a major one (aa 493-576) and a minor one (aa 535-606). The major antigenic domain maps in a region that displays a high degree of homology within a (HCV) subtype (92-97.6% identity). Yeast-encoded determinants were characterized by Western blot analysis, N-glycosidase F digestion, and using a panel of synthetic peptides. The data suggest that the major antigenic domain contains at least two determinants, one of them mimicked by an 18-mer peptide (aa 514-531). ELISA and competitive inhibition assays demonstrated that: (1) the determinants appear subtype 1a-specific, (2) seroprevalence of antibody to the determinants is rather low (20.6%), and (3) donors show a heterologous response to the different determinants. Antibody response to the E2 determinants was studied in HCV-infected chimpanzees and post-transfusion-associated NANB hepatitis cases. The antibody response was found during chronic infection and may not be effective for virus clearance.
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PMID:Characterization and mapping of a B-cell immunogenic domain in hepatitis C virus E2 glycoprotein using a yeast peptide library. 751 Apr 36

The mouse hepatitis virus (MHV) JHM strain (JHMV) produces primary demyelination in the central nervous system associated with acute encephalomyelitis. Humoral and cellular immune responses both participate in controlling the development of chronic MHV-induced demyelination. A subset of the CD8+ cytotoxic T lymphocytes (CTL) induced by immunization of BALB/c (H-2d) mice with JHMV is specific for the viral nucleocapsid protein. This CTL population recognizes an epitope located within the carboxy-terminal 149 amino acids in association with the Ld class I molecule (S. A. Stohlman, S. Kyuwa, M. Cohen, C. Bergmann, J. P. Polo, J. Yeh, R. Anthony, and J. G. Keck, Virology 189:217-224, 1992). Using a panel of vaccinia virus recombinants expressing truncated forms of the nucleocapsid protein and a series of overlapping synthetic peptides, we mapped the response to 15 amino acids. This sequence, encompassing the MHV epitope, contains the Ld-specific binding motif. The predicted 9-mer peptide (residues 318 to 326: APTAGAFFF) was sufficient and highly active in sensitizing target cells for CTL recognition when either added exogenously or synthesized intracellularly. Cross-reactivity of JHMV nucleocapsid protein-specific CTL with six other MHV strains indicated that natural sequence variations within the 9-mer epitope are tolerated in positions 4 and 5, whereas all other amino acids are conserved. These data define a novel 9-mer Ld-restricted CTL epitope which represents the first MHV CTL epitope. Characterization of this epitope provides a molecular basis to study the role of nucleocapsid protein-specific CTL in the clearance of JHMV from the central nervous system.
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PMID:Characterization of the Ld-restricted cytotoxic T-lymphocyte epitope in the mouse hepatitis virus nucleocapsid protein. 769 65

Three models for the secondary structure of the hepatitis delta virus (HDV) antigenomic self-cleaving RNA element were tested by site-directed mutagenesis. Two models in which bases 5' to the cleavage site are paired with sequence at the 3' end of the element were both inconsistent with the data from the mutagenesis. Specifically, mutations in the 3' sequence which decrease self-cleavage activity could not be compensated by base changes in the 5' sequence as predicted by these models. The evidence was consistent with a third model in which the 3' end pairs with a portion of a loop within the ribozyme sequence to generate a pseudoknot structure. This same pairing was also required to generate higher rates of cleavage in trans with a 15-mer ribozyme, thus ruling out a proposed hammerhead-like 'axehead' model for the HDV ribozyme.
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PMID:Assessment of disparate structural features in three models of the hepatitis delta virus ribozyme. 837 72

We have obtained and analyzed the 600 MHz proton NMR spectra of a 74-mer RNA derived from the catalytic domain of hepatitis delta virus genomic RNA (HDV RNA) to determine its secondary structure. Deconvolution of the NMR spectrum obtained at 32 degrees C indicates that part of the 74-mer RNA molecule may exist in multiple conformations in equilibrium. The major conformer contains two A-U base pairs and 14 +/- 2 G-C base pairs. It appears to contain no standard G-U base pairs. Our NMR melting study suggests that this conformer has at least two stem-loop regions. One of the regions has been identified to be a tetra-loop. We have assigned five imino proton resonances of the tetra-loop stem. Our data is consistent with the pseudoknot model of Perrotta and Been.
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PMID:The catalytic domain of human hepatitis delta virus RNA. A proton nuclear magnetic resonance study. 840 69

Properties of a hepatitis delta virus (HDV) RNA ribozyme system, which consists of three RNA oligomer strands (substrate 8-mer; enzyme 16-mer plus 35-mer) and contains a hybrid sequence of genomic and antigenomic RNA cores, are reported. Effects of Mg2+ concentration, divalent metal ion species, pH, and temperature on the cleavage activity were examined. The substrate cleavage activity increased with increasing Mg2+ concentration (0-100 mM). Ca2+ and Mn2+ ions were the most effective divalent cations and Mg2+ was less effective. The cleavage activity increased with increasing pH (5-7.5). The optimum temperature for the cleavage activity was 25-40 degrees C. The Mg2+ concentration, pH and temperature dependencies are different from those reported for the single-strand ribozymes (about 90-mer) although the divalent metal ion preference is very similar. Conformational change induced by Mg2+ ion titration was monitored by CD. The CD data and the activity-Mg2+ concentration data were analyzed by curve-fitting analysis using equations derived for multiple metal ion binding mechanisms. The data can be explained by a model in which three Mg2+ ions bind to one ribozyme unit.
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PMID:Properties of hepatitis delta virus ribozyme, which consists of three RNA oligomer strands. 935 86

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.
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PMID:Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vaccine development. 1049 64

Three variants of minimized hepatitis delta virus (HDV) RNA ribozyme systems (Rz-1 to approximately Rz-3) (Fig. 1) were designed on the basis of the "pseudoknot" structure model and synthesized. Rz-1 is a cis-acting ribozyme system (a cleaved form, 56-mer) in which stem IV is deleted from the active domain of genomic HDV RNA. Rz-1 was uniformly labeled with stable isotopes, 13C and 15N. The 2D-NOESY and 2D-HSQC data for Rz-1 suggest that Rz-1 forms the pseudoknot structure and G38 which is opposite to the cleavage site makes a base-pair. Rz-2 is a trans-acting ribozyme system which consists of three RNA oligomer strands (substrate: 8-mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme: 16-mer plus 35-mer). Rz-3 is a ribozyme in which the three RNA strands of Rz-2 are connected. It turns out that Rz-3 forms an inactive structure with low cleavage activity (k(obs) = 0.009) and final cleavage yield (6%). Rz-3 has the highest cleavage activity at pH 5.5. The optimal activity at acidic pH is similar to that of the wild type ribozyme. We also synthesized and examined the activity and structure of Rz-4 (designed by Perrotta and Been) which consists of two RNA strands (1).
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PMID:Design and NMR analysis of HDV ribozymes for structural investigation. 1078 Apr 59


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