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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene encoding the major core protein P22c of hepatitis B virus is preceded by a precore sequence. Expression of the core gene with the precore in Escherichia coli results in a membrane protein of HBe antigenicity. Expression in mammalian cells generates secreted HBeAg. To study the biosynthetic pathway of HBeAg and the function of precore in this process, we translated mRNAs for core proteins with and without precore using reticulocyte lysates and microsomal vesicles. The precore sequence was cleaved cotranslationally as a signal peptide, probably at alanine 19. The processed product P23e was partially translocated to the lumen of the microsomes. The arginine-rich carboxy-terminal domain of P23e was however not translocated and susceptible to trypsin. Clusters of positive-charged amino acids seem to act as a novel type of translocation stop signal. Trypsin generated a P16e which no longer had a transmembraneous configuration. The findings may explain the biosynthesis and potential function of HBeAg in hepatitis B virus-infected hepatocytes.
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PMID:Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. 335 97

Hepatitis B virus (HBV) DNA contains a precore (pre-c) sequence of 29 codons with unknown function upstream of its gene for the major core protein. Its significance was studied by expression of core proteins with and without pre-c in Escherichia coli. Core protein without pre-c, P22c, assembled spontaneously to core particles and formed core antigen. It had the same size and antigenicity as core particles from infected liver. Core protein with pre-c, P25e, instead formed membrane-associated e antigen (HBeAg). The data suggest that pre-c functions as a signal peptide for the attachment of core protein P25e to cellular membranes. This hypothesis can explain the not yet understood relation between viremia and HbeAg and the protective role of anti-HBe antibody.
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PMID:Precore sequence of hepatitis B virus inducing e antigen and membrane association of the viral core protein. 353 36

A model is proposed to explain the presence of the e antigen (HBeAg) of hepatitis B virus (HBV) in the serum of individuals infected with this virus. The e antigen, which has only recently been characterized, is a fragment of the virus core, or nucleocapsid, protein. Serum HBeAg is a valuable clinical marker for active HBV infection because its appearance correlates both with virus replication in the liver and with the presence of circulating virions. In this study a protease-like amino acid sequence was identified at the amino terminus of the core protein sequence. Experimental evidence indicates that HBeAg may be produced by proteolytic self-cleavage of the core protein.
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PMID:Proteolytic self-cleavage of hepatitis B virus core protein may generate serum e antigen. 355 7

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

Primary hepatocellular carcinoma cells (PLC/342) propagated in nude mice produce hepatitis B surface antigen of subtype adr, as well as core particles containing viral DNA and DNA polymerase. Free and integrated forms of hepatitis B virus (HBV) DNA in the tumor were isolated by molecular cloning, and their nucleotide sequences were determined. Both of the two representative clones of free HBV DNA had the same genomic length (3,158 base pairs) and had two stop codons as well as two deletions in the envelope gene. None of the seven distinct clones of integrated HBV DNA possessed the entire viral genome. The integrated clone sequences had deletions and rearrangements, and only two clones possessed the envelope gene including the promoter and enhancer sequences. The C gene, which codes for core protein, was preserved in the two free clones and one of the integrated clones. The P gene, which codes for DNA polymerase, had deletions at two positions of 21 and 36 base pairs in both free clones, but was carried in toto by one of the integrated clones. The nucleotide sequences of the S genes of two free and four integrated clones, as well as their two inverted repeats, were compared. All of the eight sequences of the S gene possessed two nucleotide substitutions in common that were not displayed by any of the reported HBV genomes. The sequences differed from one another by only 1.2%. They differed, however, from 11 reported HBV genomes of subtype adr by 2.4%, from an ayr genome by 1.9%, from 2 adw genomes by 6.9%, and from 2 ayw genomes by 5.9%. These results indicate that all free and integrated HBV DNA species in the PLC/342 tumor cell evolved from a common progenitor. The free HBV DNA underwent nucleotide substitutions during several integration events, resulting in integrated HBV DNA copies that were similar in sequence but distinct from the reported HBV genomes.
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PMID:Free and integrated forms of hepatitis B virus DNA in human hepatocellular carcinoma cells (PLC/342) propagated in nude mice. 366 52

Analysis of the serum of duck hepatitis B virus (DHBV)-infected ducks has revealed the presence of C-terminally truncated viral core proteins (e antigens). These proteins are glycosylated and therefore were not released from infected cells by lysis but rather by active secretion, indicating that the DHBV core protein can be synthesized alternatively as a cytoplasmic or a secretory protein. Transient expression of cloned wild-type DHBV DNA and of a specifically designed viral mutant in a human hepatoma cell line (Hep-G2) showed that the DHBV core gene promoter is active in differentiated human liver cells and that synthesis and secretion of the processed core proteins are dependent on the expression of the pre-C region, a small open reading frame which precedes the core gene. In addition, these experiments showed that the mechanism of core protein processing and secretion is conserved between DHBV and the human hepatitis B virus and therefore might be important for the hepatitis B virus life cycle in general. In spite of this, intrahepatic injection of the pre-C mutant into uninfected ducks resulted in viremia without concomitant e-antigen synthesis, indicating that virus formation is independent of pre-C expression.
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PMID:The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation. 368 59

To study the replication strategy of the human hepatitis B virus, the 5' end of the RNA pregenome and the initiation sites of DNA plus and minus strands have been mapped. The RNA pregenome was found to be terminally redundant by 120 nucleotides; it is initiated within the pre-C region and may also function as mRNA for synthesis of the major core protein and the hepatitis B virus reverse transcriptase. The hepatitis B virus DNA minus strand is initiated within the direct repeat sequence DR1, it contains a terminal redundancy of up to eight nucleotides, and its synthesis does not require any template switch. The DNA plus strand is primed by a short oligoribonucleotide probably derived from the 5' end of the RNA pregenome, and its synthesis is initiated close to the direct repeat sequence DR2. For its elongation to pass the discontinuity in the DNA minus strand an intramolecular template switch occurs using the terminal redundancy of this template. Thus, the route of reverse transcription and DNA replication of hepatitis B viruses is fundamentally different from that of retroviruses.
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PMID:Replication strategy of human hepatitis B virus. 380 99

The nature of the protein kinase (PK) which phosphorylates the core protein of hepatitis B virus in vitro was studied. The PK copurified with the core particles during rate zonal centrifugation and gel chromatography. It showed the same size heterogeneity as the core particles, which consisted of a main fraction of 28-nm particles and a subfraction of 22- to 26-nm particles. DNA-containing heavy core particles with a density of 1.33 to 1.35 g/ml and less endogenous PK than did the light cores. The phosphorylation reaction had a rapid initial phase (several minutes) and a slow but long-lasting second phase (many hours). The PK had a high affinity for ATP (KM = 0.5 mumol/liter). Only few of the several hundred P21.9 subunits in one core particle were phosphorylated in vitro. The only amino acid which was phosphorylated in vitro was serine. The resistance of the introduced phospho group against alkaline phosphatase showed that the PK acceptor, and probably the enzyme itself, was located inside the core particle.
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PMID:Specificity and localization of the hepatitis B virus-associated protein kinase. 680 56

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

Hepatitis B virus (HBV) capsid proteins, termed core proteins, with two- to four-amino-acid insertions were assessed for capsid formation, RNA encapsidation, and the ability to support reverse transcription of the pregenome by the polymerase molecule. Velocity sedimentation analysis of insect cell-expressed recombinant core proteins revealed that only two of the nine insertion mutant proteins formed capsids with the tight banding patterns of wild-type capsids. The remaining mutant core proteins were spread over the gradients, suggesting aggregate formation, or at the top of the gradients, suggesting lack of stable capsid formation. The mutant capsid proteins were coexpressed in Huh7 cells with an HBV genome lacking a functional core gene to test for trans complementation of HBV replication. Three of the mutant core proteins formed capsids containing HBV RNA, but only two of these contained reverse-transcribed HBV DNA. While the core protein has shown resiliency in capsid formation following insertion of foreign residues into the major B-cell epitope, several of the small insertions severely reduced the efficiency of capsid formation and inhibited capsid function.
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PMID:Insertions within the hepatitis B virus capsid protein influence capsid formation and RNA encapsidation. 747 96


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