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)

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

A cDNA fragment encompassing the 5'-terminal half of the NS1 region of the hepatitis C virus (HCV) genome was cloned. The cDNA was expressed in insect cells using a recombinant baculovirus, and a protein band of approximately 21K was identified by immunoblotting with a serum sample from a patient with chronic hepatitis C. Antibody to the protein was detected in sera from 13.4% of patients with chronic non-A, non-B hepatitis (NANBH), 20.8% of patients with liver cirrhosis and 16.8% of patients with hepatocellular carcinoma with no serum markers for hepatitis B virus infection. However, the antibody was not detected in sera from patients with acute NANBH. The prevalence of antibody to the protein encoded by the NS1 region was lower than that of antibody to the HCV core protein, but much higher than that of antibody to the envelope protein. Thus, the NS1 region of the HCV genome is suggested to encode a protein produced during the course of HCV replication.
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PMID:Expression of the amino-terminal half of the NS1 region of the hepatitis C virus genome and detection of an antibody to the expressed protein in patients with liver diseases. 137 27

Hepatitis C virus (HCV) antigen expression was examined by immunohistochemical staining in liver tissue taken at biopsy from 8 anti-HCV positive patients. Frozen liver sections were stained by indirect immunofluorescence for capsid, E2/NS1, NS3, NS4 and NS5 using polyclonal antibodies raised to synthetic peptides from these regions. The antigens E2 and NS3 were localised in scattered hepatocytes and also in cells within and around areas of inflammation. A weaker signal was observed for NS4 and NS5 and no signal was seen for capsid antigen. No staining was seen in liver tissue from 9 individuals, including 3 hepatitis B virus-positive and 2 hepatitis delta virus/positive patients, who were negative for serological markers of HCV. The specificity of the staining reaction was also confirmed by the lack of staining in HCV-positive liver samples, after the antisera was pre-adsorbed against the specific peptide. Collectively, the data suggests that HCV may not only be hepatotropic but also lymphotropic, and this may be an important factor in the pathogenesis of HCV infection.
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PMID:Localisation of hepatitis C virus proteins in infected liver tissue by immunofluorescence. 768 8

Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-alpha 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the non-responders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA.
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PMID:Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b. 769 94

The prevalence of hepatitis C virus (HCV) in Libya has been investigated by seeking evidence of HCV infection in 266 healthy Libyan subjects (147 females, 119 males; age range 1-78 years), 76 of whom were registered blood donors. None had any history of blood transfusions, surgery, homosexuality, drug misuse or other risk factor for viral hepatitis. Sera from all subjects were tested for anti-HCV antibodies by enzyme-linked immunosorbent assay against synthetic structural and non-structural HCV peptides from the HCV core, envelope, NS1, NS3/NS4 and NS5 regions. Eighteen (6.8%), all of whom were seronegative for hepatitis B surface antigen (HBsAg), were found to be anti-HCV positive (including 5 blood donors). The patterns of reactivity against the individual peptides varied between subjects as follows: core (14 subjects), envelope (11), NS1 (9), NS3/NS4 (10), and NS5 (6). Fourteen of the 18 had elevated serum aminotransferase activities (AST/ALT) but so also did 9 other subjects who were seronegative for both HBsAg and anti-HCV. Twelve of the 18 anti-HCV positive subjects, including 3 of the 5 anti-HCV positive blood donors, had circulating HCV RNA detected by the polymerase chain reaction. HCV RNA was also detected in 3 of the 9 anti-HCV negative cases with elevated AST/ALT. The finding that 21 (7.9%) of the 266 subjects had evidence of HCV infection indicates that there is a very high frequency of 'community-acquired' HCV in the normal Libyan population, and this has major implications for blood transfusion in that country.
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PMID:High prevalence of hepatitis C virus in the normal Libyan population. 797 63

The amino acid sequence for the envelope protein(s) predicted from the nucleotide sequence of the E and E2/NS1 regions of the hepatitis C virus (HCV) genome is enriched with an N-linked glycosylation site motif, Asn-X-Thr/Ser, suggesting oligosaccharide moieties are present on the virion surface. We attempted to characterize the sugar moiety on the surface of HCV virions recovered from sera of infected humans to assess the natural properties of the virus. Six kinds of lectins were used to bind HCV virions in affinity column chromatographies: RCAI, WGA, Con A, AAL, LCA, and PNA. Lectin-bound virions were identified by detecting HCV RNA in eluted chromatography fractions with a polymerase chain reaction (PCR) method. Our results showed that HCV was similar to hepatitis B virus (HBV) in characteristics of binding to lectins: HCV showed a strong binding to RCAI and WGA, weak binding to Con A, and no detectable binding to AAL, LCA, or PNA. Treatment of the HCV virion preparation with an enzyme, glycopeptidase A, or a detergent, NP-40, resulted in a significant decrease in the ability to bind these lectins. Our results suggest that asparagine-linked sugar chains are present on the surface of native virions of HCV, very similar to those for HBV.
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PMID:Demonstration of sugar moiety on the surface of hepatitis C virions recovered from the circulation of infected humans. 839 23

The development of particular vector systems for the presentation of immunogenic epitopes provides a powerful approach for the delivery of antigens. These include the core-like particles formed by recombinant bluetongue virus (BTV) capsid proteins VP3 and VP7 synthesized in insect cells by recombinant baculoviruses. Previously we have reported localization of an antigenic site on the surface of tubular structures formed by the nonstructural protein NS1 of BTV, and their potential use for epitope presentation. In this study foreign sequences ranging form 44 to 116 aa in length and representing 44 aa sequence from Clostridium difficile toxin A, 48 aa of the hepatitis B virus preS2 region, and the whole of bovine leukemia virus p15 protein were inserted at the C-terminus of BTV-10 NS1. The chimeric NS1 genes were expressed using recombinant baculoviruses and the ability of the mutated NS1 proteins to form tubules was investigated. All chimeric constructs formed tubular structures which carried the foreign antigenic sequences exposed on the surface of the tubules and were highly immunogenic. When Sf cells were coinfected with three recombinant baculoviruses expressing chimeric NS1 proteins with different epitopes, their simultaneous assembly into the same tubule was demonstrated. This observation opens up the possibility of using recombinant NS1 tubules as carriers for the delivery of multiple epitopes.
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PMID:A new form of particulate single and multiple immunogen delivery system based on recombinant bluetongue virus-derived tubules. 859 17

Variants of hepatitis B, C, and delta virus have been identified in patients both with acute and chronic infections. In the hepatitis B virus genome, naturally occurring mutations have been found in all viral genes, most notably in the genes coding for the structural envelope and nucleocapsid proteins. In the hepatitis C virus genome, the regions coding for the structural envelope proteins E1 and E2, as well as the 3'-contiguous non-structural region NS1, were found to be hypervariable. Viral variants may be associated with a specific clinical course of the infection, e.g., acute, fulminant or chronic hepatitis. Specific mutations may reduce viral clearance by immune mechanisms ('vaccine escape' and 'immune escape'), response to antiviral therapy ('therapy escape'), as well as detection ('diagnosis escape'). The exact contribution, however, of specific mutations to the pathogenesis and natural course of hepatitis B, C, or delta virus infection, including hepatocellular carcinoma development, and the response to antiviral treatment remains to be established.
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PMID:Hepatitis viruses: genetic variants and clinical significance. 950 64

Recently, three distinct genotypes (1, 2 and 3) of human parvovirus B19 (B19) have been identified. However, the characteristics and distribution of B19 genotypes in Vietnam have not been investigated. Phylogenetic analysis using 49 subgenomic NS1/VP1u regions and two coding NS1-VP1/VP2 regions has been applied to investigate the prevalence of B19 genotypes in Vietnamese patients co-infected with Hepatitis B virus. Genetic analysis of the subgenomic NS1/VP1u region of B19 revealed that two genotypes of B19 were identified in these populations, with predominance of genotype 1 (47/49, 96 %) followed by genotype 2 (2/49, 4 %), but not genotype 3. Further, phylogenetic analysis of subgenomic B19 genomes revealed two major subgroups within genotype 1 (B19-1A and B19-1B) with an estimated nucleotide difference of >5 % between each subgroup, forming different branches. The mean percentage of amino acid variation between subgroup B19-1A and B19-1B was >2 % of the NS1, VP1 and VP2 proteins. Our results indicated that two of the three known genotypes of B19 were present in Vietnamese patients, with genotype 1 predominating, and that this genotype can be classified into at least two subgroups, B19-1A and B19-1B.
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PMID:Phylogenetic analysis of human parvovirus B19, indicating two subgroups of genotype 1 in Vietnamese patients. 1696 53

In the present study, the fragment corresponding to the immunodominant epitopes of the gE gene (gEpi) from the CL15 Argentinean strain of pseudorabies virus was expressed successfully in a baculovirus-insect cell system that contained the M6 gene of Bluetongue virus, which encodes the NS1 nonstructural protein. This protein has the ability to polymerize into highly immunogenic tubules inside infected cells that can be purified at large quantities by ultracentrifugation. Previously, the NS1 protein has been expressed by fusing it to sequences derived from viruses, such as human immunodeficiency virus type 1, hepatitis B virus, bovine leukemia virus, foot-and-mouth disease virus and influenza A virus. In the present study, a recombinant protein was obtained containing the gEpi fused to NS1 (NS1-gEpi) and used it as ELISA antigen for detection of anti-gE antibodies in order to discriminate between infected and vaccinated animals. This is the first report where gEpi was expressed in this particular baculovirus-insect cell system.
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PMID:A differential ELISA based on recombinant immunodominant epitopes of the gE gene of SHV-1 in a baculovirus-insect cell system to discriminate between pigs infected naturally with pseudorabies and vaccinated pigs. 2116 43


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