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)

Vaccine escape hepatitis B virus surface antigen (HBsAg) mutants are capable of independent replication and have been implicated in acute hepatitis. We now report the detection of these mutants with changes at various positions of the antigenic 'a' determinant in human hepatocellular carcinoma (HCC). Southern blot analysis indicated that the HBsAg mutant with the Glycine to Arginine change at position 145 was integrated in HCC, whereas those with a Threonine at position 133 instead of a Methionine were identified in the serum of aggressive HCC. Further studies on HBsAg mutants in HCC should provide new insights on their involvement in the hepatocarcinogenesis.
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PMID:Detection of hepatitis B surface antigen mutants and their integration in human hepatocellular carcinoma. 1021 46

The paper reviews the development, mode of action and field of application of synthetic regulatory peptides in the pathogenetic and immunocorrective therapy of infectious and noninfectious diseases. Great progress has been made in designing new-generation small regulatory peptides by modifying the sequence of amino acid residues in the active fragments of natural hormones to change their biological activity and therapeutic properties. The original hexapeptide Arg-alpha-Asp-Lys-Val-Tyr-Arg has been designed by chemically modifying the thymic hormone Thymopoietin in positions 32-37. The agent has been called Immunofan. It is manufactured in ampoules containing 1 ml of 0.005% sterile solution for subcutaneous and intramuscular injections. The trials of Immunofan have demonstrated that it is able to restore cell immunity, the oxygen-dependent neutrophilic bactericidal system and antiviral antibody production. It decreases the levels of inflammatory mediators, such as TNF and IL-6, and activates the redox system. Included into the complex therapy of patients with cancer diseases, Immunofan enhances the body's reserve capacity to inactivate free radicals and oxidants, substantially shortens radiation and toxic reactions. Its use ensures the continuum of chemoradiotherapy. Used in the complex therapy for chronic infections (brucellosis, hepatitis B and C, opportunistic infections), Immunofan enhances antiviral and antibacterial immunity, shortens the manifestation of clinical symptoms and major syndromes of diseases.
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PMID:[Imunofan: new-generation synthetic peptide agent]. 1037 87

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. Four chimpanzees were immunized with 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chimpanzees developed antibodies to hepatitis B surface antigen (anti-HBs), they were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reacted not only with wild-type surface antigen, but also with mutant surface antigen by competition enzyme-linked immunosorbent assay (ELISA). Thus, immunization of chimpanzees with licensed recombinant hepatitis B vaccines stimulates anti-HBs that is broadly reactive and affords protection against infection with a surface gene mutant of HBV, suggesting that properly immunized individuals are not at significant risk of infection with this prototype variant strain of HBV.
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PMID:Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus. 1046 86

Assembly of replication-competent hepadnavirus nucleocapsids requires interaction of core protein, polymerase and encapsidation signal (epsilon) with viral pregenomic RNA. The N-terminal portion (aa 1-149) of the core protein is able to self-assemble into nucleocapsids, whereas the C-terminal portion (aa 150-183) is known to interact with pregenomic RNA. In this study, two hepatitis B virus (HBV) core mutants (C144Arg and C144Lys) in which the C-terminal SPRRR (Ser-Pro-Arg-Arg-Arg) motif was replaced by a stretch of arginine or lysine residues were generated to test their role in pregenome encapsidation and virus maturation. Mutant or wild-type core-expression plasmids were co-transfected with a core-negative plasmid into human hepatoma HuH-7 cells to compare trans-complementation efficiency for virus replication. Both low- and high-density capsids were present in -the cytoplasm and culture medium of HuH-7 cells in all transfections. Nucleocapsids formed by C144Arg and C144Lys, however, lost the endogenous polymerase activity to repair HBV DNA. Furthermore, in co-transfection of pHBVC144Arg or pHBVC144Lys with a plasmid which produces replication-competent nucleocapsids, the HBV DNA repairing signal was reduced 40- to 80-fold. This is probably due to formation of mosaic particles of wild-type and mutant cores. Results indicated that the SPRRR motif at the core protein C terminus is important for HBV DNA replication and maturation. Additionally, triple-plasmid transfection experiments showed that nucleocapsids containing various amounts of C144Arg and wild-type core proteins exhibited a bias in selecting a shorter pregenome for encapsidation and DNA replication. It is therefore suggested that unknown factors are also involved in HBV pregenome packaging.
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PMID:Hepatitis B virus maturation is affected by the incorporation of core proteins having a C-terminal substitution of arginine or lysine stretches. 1057 59

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the family Hepadnaviridae. Having been found in various animals (duck, heron, woodchuck, ground squirrel, and primates), hepadnaviruses must have undergone a long history of evolution and may comprise more members than currently recognized. Chimpanzees may also have their own hepadnavirus, even if it might be very close to HBV. We analyzed HBV-like sequences from three chimpanzees (Pan troglodytes) that were most likely infected during their life in Africa in the wild. Two chimpanzees (Ch256 and Ch258) possessed a viral genome of 3182 nt in length with a 33-nt deletion in the preS1 region, which could not be classified into any of the six genotypes (A-F) of human HBV but was very homologous to a previously reported isolate from a London Zoo chimpanzee. Phylogenetically distinct from the HBV-like sequences from gibbons, orangutans, and a gorilla so far reported, the Ch256 and Ch258 isolates would represent an indigenous chimpanzee HBV (tentatively ChHBV). A third chimpanzee (Ch195) had a 3212-nt genome, classifiable into the genotype E of HBV. Because HBV-E has been found mostly in Africans, Ch195 may have been infected from a human source in Africa. However, an inverse scenario is also possible: a spread of HBV-E might have occurred from chimpanzees to humans a long time ago in Africa. Analysis of the arginine-rich C-terminal region of the core protein, which is well conserved among mammalian hepadnaviruses, indicated that HBV-E/F and nonhuman primate hepadnaviruses are much closer than HBV-A/B/C/D to the hepadnaviruses of woodchuck and ground squirrel. Our results support an "ex-nonhuman primate" hypothesis for the origin of HBV.
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PMID:Full-genome sequence analyses of hepatitis B virus (HBV) strains recovered from chimpanzees infected in the wild: implications for an origin of HBV. 1064 83

Coinfection by hepatotropic viruses can occur due to the fact that hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar routes of transmission. Different clinical features of liver disease can be observed in infected patients, ranging from fulminant, acute and chronic hepatitis to hepatocellular carcinoma (HCC). The relative role of the infecting viruses in determining the final clinical picture is not yet well defined. Several reports indicate that clinical and pathological severity of liver disease among coinfected patients is increased and in patients with HCC, co-occurrence of both viruses is a common event. The potential mechanism of tumour development still remains speculative, although direct and indirect roles for both HBV and HCV have been proposed. At the molecular level, reciprocal interference of virus replication has been repeatedly described and the extent of interference is influenced by the infecting HCV genotype, genotype 1 of HCV having more efficient inhibitory activity on HBV than genotype 2. Sequence similarities between an arginine-rich nucleocapsid motif of both viruses could support these clinical observations. Concerning response rates to interferon therapy, no satisfactory results have been achieved to date, although identification of effective therapeutic schemes, based on virological status of both viruses are warranted.
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PMID:Coinfection by hepatitis B virus and hepatitis C virus. 1072 63

Hepatitis B virus (HBV) has a unique fourth open reading frame coding for a 16.5-kDa protein known as hepatitis B virus X protein (HBX). The importance of HBX in the life cycle of HBV has been well established, but the underlying molecular function of HBX remains controversial. We previously identified a proteasome subunit PSMA7 that interacts specifically with HBX in the Saccharomyces cerevisiae two-hybrid system. Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HBX and PSMA7. Analysis of the interacting domains among PSMA7, PSMC1, and HBX by deletion and site-directed mutagenesis suggested a mutually competitive structural relationship among these polypeptides. The competitive nature of these interactions is further demonstrated using a modified yeast two-hybrid dissociator system. The crucial HBX sequences involved in interaction with PSMA7 and PSMC1 are important for its function as a transcriptional coactivator. HBX, while functioning as a coactivator of AP-1 and acidic activator VP-16 in mammalian cells, had no effect on the transactivation function of their functional orthologs GCN4 and Gal4 in yeast. Overexpression of PSMC1 seemed to suppress the expression of various reporters in mammalian cells; this effect, however, was overcome by coexpression of HBX. In addition, HBX expression inhibited the cellular turnover of c-Jun and ubiquitin-Arg-beta-galactosidase, two well known substrates of the ubiquitin-proteasome pathway. Thus, interaction of HBX with the proteasome complex in metazoan cells may underlie the functional basis of proteasome as a cellular target of HBX.
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PMID:Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex. 1074 18

Among the three related L, M, and S envelope proteins of the hepatitis B virus (HBV), the L and S polypeptides are required for virion production. Whereas the pivotal function of the pre-S region of L in nucleocapsid envelopment has been established, the contribution of its S domain and the S protein is less clear. In this study, we evaluated the role of the cytosolic S loop, common to L and S, in HBV assembly by performing mutagenesis experiments. To distinguish between the effect of the mutations on either envelope or virion formation, we investigated the ability of the mutants to assemble into secretable subviral empty envelopes and to replace the wild-type proteins in virion maturation, respectively. Virion production was found to be blocked by each of the secretion-competent deletion and substitution mutants SDelta35-39, SDelta40-46, SDelta50-56, and Svarsigma56-59, while an insertion within the loop is tolerated. Surprisingly, single mutations of the arginines terminating the loop had an opposite effect: while a conservative exchange of Arg-73 still allowed virion formation, the same mutation of Arg-79 did not. The critical sequences and/or structural requirements of the cytosolic S loop involved in nucleocapsid envelopment primarily act in the S background. These findings can be related to a model for a synergistical function of both L and S proteins in HBV morphogenesis.
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PMID:Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins. 1079 95

A conformationally biased decapeptide agonist of human C5a anaphylatoxin (YSFKPMPLaR) was used as a molecular adjuvant in stimulating an Ag-specific CTL response against murine P815S target cells expressing an Ld-restricted CTL epitope of the hepatitis B surface Ag (HBsAg). Groups of BALB/c mice (H-2d) were immunized with aqueous solutions of the HBsAg CTL epitopes (IPQSLDSWWTSL and IPQSLDSWWTSLRR); the C5a agonist (YSFKPMPLaR); the C5a agonist and HBsAg CTL epitopes admixed (IPQSLDSWWTSL and IPQSLDSWWTSLRR + YSFKPMPLaR); the C5a-active, HBsAg CTL epitope-C5a agonist constructs (IPQSLDSWWTSLYSFKPMPLaR, IPQSLDSWWTSLRRYSFKPMPLaR, and IPQSLDSWWTSLRVRRYSFPMPLaR); a C5a-inactive, reverse-moiety construct (YSFKPMPLaRRRIPQSLDSWWTSL); and a C5a-attenuated, carboxyl-terminal-blocked construct (IPQSLDSWWTSLRRYSFKPMPLaRG). Ag-specific CD8+ CTL responses were observed after the secondary boost in the absence of any added adjuvant only in mice that were immunized with C5a-active contructs, IPQSLDSWWTSLRRYSFKPMPLaR and IPQSLDSWWTSLRVRRYSFKPMPLaR. These two C5a-active immunogens contained potential subtilisin-sensitive linker sequences between the HBsAg CTL epitope and the C5a agonist; i.e., a double-Arg (RR) and a furin protease sensitive sequence (RVRR). The introduction of these potentially cleavable sequences may be a method of increasing the likelihood of liberating the CTL epitope from the C5a agonist by intracellular proteases, thereby facilitating entry of the epitope into Ag-processing pathways via an exogenous route.
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PMID:Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant. 1079 17

The S nucleotide sequences of five hepatitis B virus strains isolated from plasma samples of Tunisian patients with chronic hepatitis B were determined; the preS2 region of three of them were sequenced. According to the comparative analysis of S peptide sequences with the reported sequences in the database bank, the five hepatitis B strains were shown to be related to the D genotypic group, subtype ayw. The nature of residues at positions 125 and 127 allowed us to distinguish between each subtype of the D group and to class all five Tunisian sequences in the 'ayw2' subtype. Moreover, two of them (1366 and 523) contained a substitution of the invariant Cys69 by Arg and Cys221 by Phe, respectively. Potential structural modifications due to the Cys-Arg change are discussed.
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PMID:Genotyping of Tunisian hepatitis B virus isolates based on the sequencing of preS2 and S regions. 1088 11


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