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)

A DNA fragment, coding for hepatitis core antigen (HBcAg), was amplified by polymerase chain reaction and inserted into a lambda PL promoter-derived expression vector. The recombinant plasmid was transformed into Escherichia coli and proteins produced after heat induction were analyzed. In addition to the 21 kDa HBcAg protein, several smaller related polypeptides, particularly one of 17 kDa in size, were also detected with rabbit anti-HBcAg antiserum. Whether the protease-like sequence of core protein involved in the self-cleavage process to form the 17 kDa polypeptide was investigated by a deletion experiment. Our results with a mutant in which 7 amino acids of the conserved protease-like region in the core protein have been deleted suggest that the cleavage does not depend on the presence of these protease-like sequence. In addition, the core protein synthesized from in vitro translation reaction was not cleaved. Core particles from E. coli lysate were purified by sucrose and cesium chloride density gradient centrifugations and subsequently treated with 0.2% of SDS and 0.2% of beta-mecaptoethanol. Immunoblotting analysis, however, did not reveal any conversion of the 21 kDa protein to smaller ones. In conclusion, our results suggest that the protease-like domain at the N-terminus of the core protein does not contain intrinsic autocleavage activity, nor could the HBcAg be converted to smaller antigens by detergent treatment.
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PMID:Protease-like sequence in hepatitis B virus core antigen is not involved in the cleavage processes of core protein in Escherichia coli. 193 70

The sequences of the core proteins from several serotypes of human hepatitis B virus and related mammalian and avian hepadnaviruses are aligned with the vp3 capsid protein of mengo virus, a picornavirus. The homology indicates an eight-stranded antiparallel beta-barrel fold for the hepatitis protein, as observed in the tertiary structure of the picornavirus protein. The locations of known antigenic sites and other modifications are consistent with this structure for the core protein. The predicted folding suggests additional exposed antigenic sites and supports an evolutionary relationship between this family of enveloped DNA viruses and enveloped and non-enveloped RNA viruses.
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PMID:A model for the hepatitis B virus core protein: prediction of antigenic sites and relationship to RNA virus capsid proteins. 245 12

Integration and transcription of woodchuck hepatitis virus DNA were studied by Southern and Northern blot analysis in 26 hepatocellular carcinomas and in adjacent nontumor tissue of woodchucks (Marmota monax). All liver tissue chronically infected with woodchuck hepatitis virus contained various amounts of episomal and replicative forms of woodchuck hepatitis virus DNA: episomal and replicative forms of woodchuck hepatitis virus DNA without integration were found in six tumors, episomal and integrated woodchuck hepatitis virus DNA was observed in 18 tumors and exclusively integrated woodchuck hepatitis virus DNA was found in two tumors. In most tumors and in all of the liver tissues chronically infected with woodchuck hepatitis virus, two major woodchuck hepatitis virus RNA species (3.7 and 2.1 kilobases) were detected. In tumors of two other animals (HW76 and HW89) with integrated woodchuck hepatitis virus DNA, only single major transcripts of 3.5 and 2.5 kilobases, respectively, were detected. Hybridization with subcloned woodchuck hepatitis virus DNA probes showed that both aberrant transcripts lacked the C gene and a part of the pre-S1 gene; characterization of corresponding integrated woodchuck hepatitis virus DNA sequences revealed that the C gene was deleted in one tumor, although not in the other. In agreement with the nucleic acid data, we found expression of core protein by Western blotting only in chronically infected liver tissue of these animals, but not in the corresponding tumors. Deletion of the C gene in mRNA may be due to deletion of this gene in the integrated sequences or due to transcriptional regulation.
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PMID:Characterization of woodchuck hepatitis virus DNA and RNA in the hepatocellular carcinomas of woodchucks. 254 90

Woodchucks were immunized with recombinant woodchuck hepatitis virus (WHV) core antigen (WHcAg) to investigate whether such immunization protects against WHV infection. The C gene was cloned into a pUC12 vector and expressed in Escherichia coli. Core particles purified by sucrose and CsCl gradient centrifugation had a buoyant density of 1.37 g/ml which corresponded to the density of WHcAg particles present in chronically infected liver. Two animals immunized with the recombinant antigen developed high antibody titres and were protected against infection after challenge with WHV. The surface antigen (WHsAg) and WHV DNA were not detected in the sera of immunized animals after challenge and these animals did not develop anti-WHs. Three control animals developed a typical WHV infection. The protection from WHV infection may depend not on the presence of antibodies against the core protein but on a cellular immune response to WHcAg.
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PMID:Protection of woodchucks from infection with woodchuck hepatitis virus by immunization with recombinant core protein. 276 30

The core gene of hepatitis B virus contains two in-phase AUG codons which may both be used in the viral life cycle. By in vitro translation of transcripts produced in vitro, we investigated the corresponding core gene products and their counterparts in vivo. Depending on the location of the 5' end of the transcripts, two major core gene-derived proteins were obtained. In transcripts with both in-phase AUGs, only the first one was efficiently used and resulted in synthesis of a 25-kilodalton protein (precore). This protein contains a leader sequence and could be cotranslationally processed to a protein of 22.3 kilodaltons. Translation of transcripts lacking the first AUG of the core gene produced a core protein of 21.5 kilodaltons which comigrated with the core antigen expressed in infected livers. These data suggest that the major nucleocapsid protein expressed in vivo is initiated at the second ATG of the C gene and that a precore protein is probably synthesized as a precursor protein which is cotranslationally processed. Proteins consistent in size with processed and unprocessed precore proteins detected in woodchuck hepatitis virus-infected livers support this conclusion.
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PMID:Expression of the hepatitis B virus core gene in vitro and in vivo. 362 40

The complete nucleotide sequence of a woodchuck hepatitis virus genome cloned in Escherichia coli was determined by the method of Maxam and Gilbert. This sequence was found to be 3,308 nucleotides long. Potential ATG initiator triplets and nonsense codons were identified and used to locate regions with a substantial coding capacity. A striking similarity was observed between the organization of human hepatitis B virus and woodchuck hepatitis virus. Nucleotide sequences of these open regions in the woodchuck virus were compared with corresponding regions present in hepatitis B virus. This allowed the location of four viral genes on the L strand and indicated the absence of protein coded by the S strand. Evolution rates of the various parts of the genome as well as of the four different proteins coded by hepatitis B virus and woodchuck hepatitis virus were compared. These results indicated that: (i) the core protein has evolved slightly less rapidly than the other proteins; and (ii) when a region of DNA codes for two different proteins, there is less freedom for the DNA to evolve and, moreover, one of the proteins can evolve more rapidly than the other. A hairpin structure, very well conserved in the two genomes, was located in the only region devoid of coding function, suggesting the location of the origin of replication of the viral DNA.
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PMID:Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence. 708 58

Antibodies to the hepatitis C virus (HCV) core of various immunoglobulin classes were determined by enzyme immunoassays with three synthetic peptides, CP14 (amino acids 5-40 of the core protein), CP10 (5-23), and CP9 (39-74). In 135 patients with chronic type C liver disease, anti-CP14, anti-CP10, and anti-CP9 of IgG class were detected in 99%, 94%, 82%, respectively; those of IgM class in 86%, 69%, and 39%; and those of IgA class in 56%, 40%, and 4%. Thus anti-CP14 was more prevalent than anti-CP10 or anti-CP9 in every immunoglobulin class. The prevalence of IgM anti-CP14 was much higher (P < 0.001) in patients (116/135 or 86%) than in asymptomatic carriers of HCV (13/39 or 33%). In seven patients with acute hepatitis C, IgM anti-CP14 continued to decrease in two in whom hepatitis resolved, but increased in five in whom hepatitis once resolved and then exacerbated. IgM anti-CP14 was followed in 30 patients with chronic hepatitis C during 24 weeks while they received recombinant interferon alpha-2a. IgM anti-CP14 decreased remarkably within 8 weeks in all of them. Thereafter, it continued to decrease in nine patients who responded to interferon and lost HCV RNA from circulation, but started to increase in five non-responders who continued to have high titers of HCV RNA. In the remaining 16 patients in whom HCV RNA decreased once and then increased, IgM anti-CP14 continued to decrease till 20 weeks and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IgM antibody to a hepatitis C virus core peptide (CP14) for monitoring activity of liver disease in patients with acute or chronic hepatitis C. 751 23

Antibody subclasses directed against the core protein (HCc) of hepatitis C virus (HCV) were measured in 27 patients with acute non-A, non-B (NANB) hepatitis, and 99 patients with chronic HCV-associated liver disease. IgM, IgA, and IgG anti-HCc responses were observed in 11 (40.7%), 7 (25.9%), and 18 (67%) patients with acute NANB hepatitis, respectively. Twenty-four (24.2%) and 40 (40.4%) patients with chronic HCV infection also had detectable IgM and IgA, respectively. IgM anti-HCc inconsistently detected acute infection, and HCV ribonucleic acid (RNA) could be detected preceding the rise in anti-HCc antibodies in five consecutive patients with acute hepatitis. IgM anti-HCc also could not distinguish acute from chronic infection and did not correlate with histologic progression. However, the form of IgA present (polymeric vs monomeric) did discriminate acute from chronic infection and the IgA anti-HCc titer correlated with histologic evidence of liver disease in patients with chronic HCV infection.
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PMID:IgM and IgA antibodies generated against hepatitis C virus core antigen in patients with acute and chronic HCV infection. 752 23

Hepatitis C virus (HCV) is a main causative agent for transfusion-associated and sporadic cases of non-A, non-B hepatitis throughout the world. HCV has a positive-strand RNA of about 9,400 nucleotides as its genome, whose organization is similar to those of animal pestiviruses or human flaviviruses. In spite of the lack of an effective replication system in tissue culture cells, genes coding for viral proteins of HCV have been identified. The putative nucleocapsid (p22) and envelope (gp35 and gp60) proteins have been expressed in cells by different vectors under various foreign promoters. Furthermore, a truncated core protein and association of envelope proteins with nonstructural proteins have also been observed. These synthesized viral proteins have been shown to be useful for diagnostic assays.
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PMID:Characterization of HCV structural proteins expressed in various animal cells. 752 19

Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype 1b) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype 1b. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region. It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-alpha treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-gamma production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection. 755 51


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