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)

Localization of woodchuck hepatitis virus in liver tissue from 10 infected woodchucks was investigated immunohistochemically and ultrastructurally. Woodchuck hepatitis virus surface antigen was detected by immunoperoxidase methods in the cytoplasm of hepatocytes with a fine granular and/or inclusion body appearance. Woodchuck hepatitis virus surface antigen positive hepatocytes were often found in the peripheral zone of hepatic lobules. In contrast to human hepatitis B core antigen, woodchuck hepatitis virus core antigen was observed only in the cytoplasm of hepatocytes, but not in the nuclei. In hyperplastic foci, woodchuck hepatitis virus antigen-positive hepatocytes were found in 3 of 8 animals. Furthermore, in 1 of 5 animals with hepatocellular carcinoma, woodchuck hepatitis virus surface antigen and woodchuck hepatitis virus core antigen were present in carcinoma cells. Electron microscopic examination revealed many filamentous structures (18 to 20 nm in diameter) in the cisternae of the endoplasmic reticulum. Noncoated core particles (18 to 20 nm in diameter) were found in the cytoplasm of the hepatocytes, but not in the nuclei. The coated particles (42 to 45 nm in diameter) were observed in the cisternae of the endoplasmic reticulum. These coated particles were shown to be morphologically identical to the virus particles in serum. These results indicate that woodchuck hepatitis virus core antigen is produced and assembled mainly in the cytoplasm of hepatocytes, and seems to be rapidly assembled into virion. The similarity of woodchuck hepatitis virus infection to human hepatitis B virus infection makes the woodchuck an excellent experimental model for the study of hepadna virus oncogenesis.
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PMID:Localization of woodchuck hepatitis virus in the liver. 327 92

The major hepatitis B virus (HBV) core protein is a viral structural protein involved in nucleic acid binding. Its coding sequence contains an extension of 29 codons (the "precore" region) at the amino terminus of the protein which is present in a fraction of the viral transcripts. This region is evolutionarily conserved among mammalian and avian HBVs, suggesting it has functional importance, although at least for duck HBV it has been shown to be nonessential for replication of infectious virions. Using in vitro assays for protein translocation across the endoplasmic reticulum membrane, we found that the precore region of the HBV genome encodes a signal sequence. This signal sequence was recognized by signal recognition particle, which targeted the nascent precore protein to the endoplasmic reticulum membrane with efficiencies comparable to those of other mammalian secretory proteins. A 19-amino acid signal peptide was removed by signal peptidase on the lumenal side of the microsomal membrane, generating a protein similar to the HBV major core protein, but containing 10 additional amino acids from the precore region at its amino terminus. Surprisingly, we found that 70-80% of this signal peptidase-cleaved product was localized on the cytoplasmic side of the microsomal vesicles and was not associated with the membranes. We conclude that translocation was aborted by an unknown mechanism, then the protein disengaged from the translocation machinery and was released back into the cytoplasm. Thus, a cytoplasmically disposed protein was created whose amino terminus resulted from signal peptidase cleavage. The remaining 20-30% appeared to be completely translocated into the lumen of the microsomes. A deletion mutant lacking the carboxy-terminal nucleic acid binding domain of the precore protein was similarly partitioned between the lumen of the microsomes and the cytoplasmic compartment, indicating that this highly charged domain is not responsible for the aborted translocation. We discuss the implications of our findings for the protein translocation process and suggest a possible role in the virus life cycle.
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PMID:Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. 328 45

An attempt was made to infect primary duck hepatocyte cultures with duck hepatitis B virus in vitro in order to clarify the biology of hepatitis B virus. Livers of ducklings, 0 to 17 days posthatch, without viremia were digested ex situ by perfusion of collagenase solution through the portal or hepatic vein. Homogeneous hepatocyte suspensions were seeded into plastic dishes in L-15 medium containing 10(-8) M insulin, 2 X 10(-8) M glucagon and 10(-8) M dexamethasone and were subsequently inoculated with sufficient numbers of duck hepatitis B virus. As a result, duck hepatitis B virus multiplication started weakly on Day 2, gradually increased and reached the maximum level approximately on Day 10 postinoculation. Viral replication was revealed by duck hepatitis B virus DNA in the cell pellet and in the culture medium and duck hepatitis B virus DNA-specific transcripts in the cell pellet. Immunostaining demonstrated duck hepatitis B virus core antigen in approximately 10% of cultured hepatocytes, and an increase in numbers of positive cells was not observed with time for up to 18 days of culture. Viral particles were found within the endoplasmic reticulum, and the inoculation of culture medium provoked viremia in the ducklings. The age of ducklings did not influence the numbers of cells infected. The in vitro infection system was similar to the in vivo one; however, the former seemed to be age-independent and to allow replication of duck hepatitis B virus in the limited number of hepatocytes.
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PMID:In vitro transmission of duck hepatitis B virus to primary duck hepatocyte cultures. 329 62

In order to evaluate geographical differences in the liver pathology of ducks infected with duck hepatitis B virus (DHBV), ducks in Chiba and Shimane, Japan, and Shanghai, China, were investigated. The numbers (DHBV positive/negative) and the maximum age of the ducks examined were 18/10 at 19 mo, 15/1 at 3 yr 4 mo, and 72/27 at 18 mo, respectively. DHBV infection was induced experimentally in ducks from Chiba and Shimane but was present congenitally in those from Shanghai. Ducks were examined regarding liver function tests, conventional histology, immunohistology, electron microscopy, and molecular hybridization for DHBV DNA in the serum and liver. There was no significant difference between DHBV-positive and -negative ducks in bilirubin and transaminase and alkaline phosphatase activities in the sera. Histologically, while the livers of ducks from Chiba and Shimane did not show necroinflammatory (hepatitis) activity, those from Shanghai frequently did (52.5%). Necroinflammatory activity of the Shanghai ducks was present almost equally in both DHBV-positive and -negative livers. The livers of Shanghai ducks but not the other two areas often (8.3%) had ground-glass inclusions which corresponded ultrastructurally to numerous virus particles in the dilated cisternae of the proliferated endoplasmic reticulum. No advanced liver disease, such as cirrhosis or hepatocellular carcinoma, was observed. There was no significant difference in the amount of DHBV DNA in the sera or in its pattern in the liver tissue among ducks of the three areas. In addition, the livers of Chiba ducks frequently had amyloidosis, while those of Shanghai ducks were contaminated with parasites. In conclusion, DHBV infection did not appear to provoke significant hepatitis activity or advanced liver disease in the examined ducks of all three areas, and the DHBV-positive livers from Shanghai ducks showed a different morphological appearance from those of the other two areas. This variation might reflect the difference in the strain of ducks, subtypes of DHBV, environmental factors, or a combination of these influences.
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PMID:Geographical pathology of duck livers infected with duck hepatitis B virus from Chiba and Shimane in Japan and Shanghai in China. 334 10

Overproduction of the hepatitis B virus (HBV) large envelope polypeptide by transgenic mice containing the entire HBV envelope coding region leads to the formation of extremely long (up to 800 nm), occasionally branching, filamentous 22-nm-diameter hepatitis B surface antigen particles that accumulate within the endoplasmic reticulum of the hepatocyte and are not efficiently secreted. As the endoplasmic reticulum expands to accommodate the increasing cellular filament stores, the hepatocytes become enlarged, hydropic, and eosinophilic and also display the characteristic features of "ground-glass" cells. As filament storage progresses, the ground-glass cells undergo coagulative necrosis and the mice develop an age-dependent lesion, whose severity is related to the intracellular concentration of envelope polypeptide, that is characterized by focal hepatocellular degeneration and necrosis, lobular macrophagic inflammation, and increased serum transaminase activity. Advanced lesions demonstrate hepatocellular hyperplasia evident as lobular architectural disarray and microscopic hepatocellular nodules, many of which no longer contain detectable HBV envelope antigens. These changes may become extreme, producing a massively enlarged liver due to multifocal nodular regenerative hyperplasia. Overproduction of the large HBV envelope polypeptide exerts major structural constraints on HBV particle formation, leading to reduced secretion and progressive intracellular accumulation of hepatitis B surface antigen, which can reach sufficiently high concentrations to be directly cytotoxic to hepatocytes in this transgenic mouse system.
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PMID:Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. 347 14

A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen.
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PMID:Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee. 351 26

Hepatitis B surface antigen (HBsAg) particles are secreted by Chinese hamster ovary cells that are stably transfected with the S gene of hepatitis B virus. The assembly of HBsAg into cylindrical and spherical particles occurred intracellularly within the endoplasmic reticulum. HBsAg particles accumulated within large dilated areas of the endoplasmic reticulum and remained within these structures for most of the time prior to secretion from the cells. Once the particles were formed, the HBsAg polypeptides did not appear to become associated with subsequent intracellular organelle membranes or the plasma membrane. HBsAg within the dilated structures did not bind wheat germ agglutinin, indicating that its oligosaccharide chains had not yet been processed to the complex form (containing terminal sialic acid-N-acetylglucosamine residues). The oligosaccharide chains of HBsAg are processed to the complex form and can be detected on the HBsAg after secretion, but this event was not detected within cells. In addition, HBsAg was not observed on the cell surface by indirect immunofluorescence or immunoprecipitation, although immunoelectron microscopy revealed some staining at or near the cell surface. These results suggested that HBsAg was either secreted from cells without being incorporated into the plasma membrane, or that the levels of HBsAg in the plasma membrane were below the limits of detection.
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PMID:Intracellular assembly and packaging of hepatitis B surface antigen particles occur in the endoplasmic reticulum. 351 85

A sequential study was performed to investigate the occurrence and localization of duck hepatitis B virus in the liver of domestic ducks utilizing the indirect immunoperoxidase method and electron microscopy. Seventeen ducklings were injected intravenously with duck hepatitis B virus-positive serum within 24 hr after hatching and were subsequently sacrificed on the 2nd, 3rd, 4th, 5th, 27th and 44th day after injection. Nine ducklings were not injected and were used as a negative control. Duck hepatitis B virus DNA by spot hybridization using a [3P]-labeled probe occurred in trace amounts on the 2nd day and in large amounts on the 4th day after inoculation. Immunoreactivity for DHBV was seen in the hepatocytes, sporadically on the 2nd day and diffusely on the 4th day, and also in the biliary epithelial cells on the 27th day. Both kinds of cells revealed staining in the cytoplasm but not in the nucleus. Virus particles were recognized by electron microscopy in the hepatocytes beginning on the 4th day. The hepatocytes had many incomplete virus particles, 40 to 61 nm in diameter, and a few complete virus particles, 40 nm in diameter, in the cisternae of the rough and smooth endoplasmic reticula. Such particles and the endoplasmic reticulum showed reaction products for duck hepatitis B virus by immunoelectron microscopy. There were clusters of core particles, 27 nm in diameter, in the hyaloplasm around peroxisomes where an assembly of cores appeared to occur. No conspicuous virus particles were recognized in the biliary epithelial cells. The similarities and differences in virus localization between duck hepatitis B virus and hepatitis B virus are discussed.
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PMID:Occurrence and ultrastructural localization of duck hepatitis B virus in the liver of ducks after experimental infection. 380 3

A 14-month old female Pekin duck experimentally infected as an embryo with duck hepatitis B virus via the amniotic route has been a chronic carrier of duck hepatitis B virus with very high (P/N) values of DNA polymerase activity since hatching. All the progeny were, on evaluation for congenital infection, found to be duck hepatitis B virus positive by endogenous DNA polymerase reaction and electron microscopy. These offspring remained persistently viremic throughout the study. Maternal transmission therefore bred true to a total of 49 offspring--24 ducklings (less than 24 hr old) and 25 ducks--studied. Six of these 25 ducks matched for age and sex and bled weekly for 6 weeks exhibited fluctuating plasma levels of DNA polymerase activity. Higher DNA polymerase activity was detected in newly hatched ducklings than in older viremic ducks. This observation was corroborated with the results of electron microscopic examination of thin sections of liver. Duck hepatitis B virus particles, located within vesicles of rough endoplasmic reticulum in the cytoplasm of hepatocytes, were more abundant, and therefore more readily observed, in ducklings than in older ducks.
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PMID:Maternal transmission of duck hepatitis B virus in pedigree Pekin ducks. 401 33

Liver specimens from 1-day-old ducklings infected in ovo with maternally transmitted duck hepatitis B virus (DHBV) were examined by electron microscopy. Complete and incomplete DHBV particles were located within hypertrophied cisternae of the endoplasmic reticulum of the hepatocytes. The complete viral particles found intracellularly have inner cores with a diameter ranging from 35 to 37.5 nm and an outer coat or envelope. The whole particle measures approximately 45-65 nm in diameter. Naked core particles were located in the nuclei, free in the cytoplasm, and also near or on the cisternal membrane of the endoplasmic reticulum on the cytoplasmic face. Duck hepatitis B virions appear to share morphological characteristics with the viral coat and core of human hepatitis B virus (HBV). Electron microscopy suggested that the core particles of DHBV migrate from the nucleus into the cytoplasm through the nuclear pores. The complete viral particles are probably formed by protrusion of the core particles through the endoplasmic reticulum and by simultaneous encapsulation with a coat derived from the endoplasmic reticulum.
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PMID:Studies by electron microscopy on the assembly of duck hepatitis B virus in the liver. 404 31


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