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)

Hepatitis B virus (HBV) particles are generated by budding of preformed cytoplasmic nucleocapsids into endoplasmic reticulum (ER) membranes containing the three viral envelope proteins (L, M, and S). We have examined the contributions of the envelope proteins to virion assembly by using cultured hepatoma cells transfected with mutant HBV genomes bearing lesions in the envelope coding regions. We show here that HBV nucleocapsids are not released from cells without expression of envelope proteins, implying an active role for these proteins in viral morphogenesis. S and L but not M proteins are necessary for virion production. L protein over-expression inhibits virion release, just as it inhibits the release of subviral hepatitis B surface antigen (HBsAg) particles. Mutant L proteins that are no longer capable of retaining HBsAg particles in the ER still allow virion formation, indicating that this ER retention reaction is not required for viral budding. Myristoylation of L protein is also dispensable for virion formation. A chimeric protein bearing foreign epitopes fused to the S protein can be incorporated into virions when coexpressed with the wild-type envelope proteins. Models for the dependence of virion formation on both L and S proteins are discussed.
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PMID:The role of envelope proteins in hepatitis B virus assembly. 199 57

The coding sequences for each of the three envelope proteins of hepatitis B virus (HBV), the major (S), middle (M), and large (L) surface proteins, were expressed in Saccharomyces cerevisiae. Analysis by immunoelectron microscopy of thin sections of yeast cells showed that production of L protein but not of M or S protein provoked morphological changes in the yeast endoplasmic reticulum. A large accumulation of membranous structures connected with the perinuclear cysternae and specifically labeled by a monoclonal antibody directed against the amino-terminal (preS1) sequence of the L protein, was observed. The L protein was post-translationally modified by N- and O-linked glycosylation, indicative of its entry into the yeast secretory pathway and by N-myristoylation of its amino-terminal glycine residue. Deletion of this glycine residue resulted in the synthesis of a nonmyristoylated L protein. Proliferation of the endoplasmic reticulum was comparable in cells producing either the myristoylated or nonmyristoylated L protein, indicating that myristoylation alone is not responsible for the induction of the abnormal membrane morphology.
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PMID:The large surface protein of hepatitis B virus is retained in the yeast endoplasmic reticulum and provokes its unique enlargement. 201 79

Cells infected with hepatitis B virus produce both virions and 20-nm subviral (surface antigen or HBsAg) particles; the latter are composed of viral envelope proteins and host-derived lipid. Although hepatitis B virus encodes three envelope proteins (L, M, and S), all of the information required to produce an HBsAg particle resides within the S protein. This polypeptide spans the bilayer at least twice and contains three hydrophobic regions, two of which are known to harbor topogenic signal sequences that direct this transmembrane orientation. We have examined the effects of mutations in these and other regions of the S protein on particle assembly and export. Lesions in the N terminal signal sequence (signal I) can still insert into the endoplasmic reticulum bilayer but do not participate in any of the subsequent steps in assembly. Deletion of the major internal signal (signal II) completely destabilizes the chain. Deletion of the C-terminal hydrophobic domain results in a stable, glycosylated, but nonsecreted chain. However, when coexpressed with wild-type S protein this mutant polypeptide can be incorporated into particles and secreted, indicating that the chain is still competent for some of the distal steps in particle assembly. The correct transmembrane disposition of the N terminus of the molecule is important for particle formation: addition of a heterologous (globin) domain to this region impairs secretion, but the defect can be corrected by provision of an N-terminal signal sequence that restores the proper topology of this region. The resulting chimeric chain is assembled into subviral particles that are secreted with normal efficiency.
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PMID:Mutational analysis of hepatitis B surface antigen particle assembly and secretion. 204 Oct 95

Liver specimens from Shanghai Ma ducks infected with duck hepatitis B virus (DHBV) were examined by immunohistochemical technique and electron microscopy. The results showed that DHBV and DHBV antigen were found not only in the hepatocytes but also in the biliary epithelial cells of infected ducks. Electron microscopy also revealed that incomplete spherical particles, 40-50 nm in diameter, were present in the dilated cisternae of rough endoplasmic reticulum (RER), and complete spherical virions, 55-65 nm in diameter, existed in the cytoplasmic vesicles and cytoplasm in small amounts. The results of the present study seem to confirm the possibility of infection and replication of DHBV not only in the liver cells but also in the biliary epithelial cells of ducks.
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PMID:[Ultrastructural study of duck hepatitis B virus in biliary epithelial cells of duck liver]. 208 53

Liver specimens from the Shanghai Ma ducks congenitally infected with duck hepatitis B virus (DHBV) were examined by immunohistochemical technique and electron microscopy. All the 12 serum DHBV positive ducks showed varying degrees of positive straining in hepatocytes. In 8 of the 12 ducks, DHBV antigen was discovered in the cytoplasm of biliary epithelial cells. Conventional electron microscopy revealed two kinds of virus particles in the biliary epithelial cells: 1. the incomplete virus, 40-50 nm in diameter and spherical in shape with an outer membrane, located mainly in the dilated cisternae of rough endoplasmic reticulum of the cells in large amounts; 2. the complete virions, 55-60 nm in diameter, were spherical with an outer membrane and located mainly in the cytoplasmic vesicles in small amount. We believe the particles found in the biliary epithelial cells in this study were DHBV particles. It is most likely that the infection and replication of DHBV not only take place in the liver cells but also in the biliary epithelial cells.
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PMID:Ultrastructural study of hepatitis B virus in biliary epithelial cells of duck liver. 211 56

Hepatocytes respond to injury by a few basic pathological reactions that are reflected in cell death, different types of degeneration, regeneration, or tumorous transformation. At the ultrastructural level, alterations of cell organelles can be observed in different combinations as a result of the injury, depending on the etiological agent(s) or pathological conditions developed. Nuclear bodies, dilation and fragmentation of rough endoplasmic reticulum (rer), swelling of mitochondria, and an increased number of lysosomes occur during acute viral hepatitis. The core and surface components of the hepatitis B virus can be localized in the liver cells in chronic hepatitis and in carriers. Close contact of hepatocytic and lymphocytic cell membranes were observed in chronic active hepatitis. Hepatocytes surrounded by an increased amount of collagen fibers are characteristic of cirrhosis. Loosely arranged, fine fibrils or condensed forms of Mallory bodies are pathognomic for alcoholic injury. A wide spectrum of alterations are noted after drug treatment: the proliferation of smooth endoplasmic reticulum (ser) as an adaptive phenomenon, focal or complete necrosis of the cell, inflammation, and the like. The fine structural analysis of hepatocytic inclusions in storage diseases has a differential diagnostic value. The storage of copper and other elements can be measured by x-ray microanalysis. The study of the hepatocytic differentiation in liver tumors is highly important in establishing the diagnosis and in proving the hepatocytic origin of the tumor.
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PMID:Fine structure of hepatocytes during the etiology of several common pathologies. 218 62

The coding region for the hepatitis B virus surface antigens contains three in-phase ATG codons which direct the synthesis of three related polypeptides. The 24-kilodalton major surface (or S) glycoprotein is initiated at the most distal ATG and is a transmembrane protein whose translocation across the bilayer is mediated by at least two uncleaved signal sequences. The product of the next upstream ATG is the 31-kilodalton pre-S2 protein, which contains 55 additional amino acids attached to the N terminus of the S protein. This pre-S2-specific domain is translocated into the endoplasmic reticulum. Using a coupled in vitro translation-translocation system, we showed that (i) the pre-S2 domain itself lacks functional signal sequence activity, (ii) its translocation across the endoplasmic reticulum membrane is mediated by downstream signals within the S domain, and (iii) the N-terminal signal sequence of the S protein can translocate upstream protein domains in the absence of other signals. The hepatitis B virus pre-S2 protein is an example of a natural protein which displays upstream domain translocation, a phenomenon whose existence was originally inferred from the behavior of synthetic fusion proteins in vitro.
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PMID:The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences. 230 50

Hepatitis B virus core antigen gene expresses two cocarboxy-terminal proteins, termed precore and core proteins. Both precore and core proteins can form nucleocapsid-like particles. In order to understand the mechanism that leads to the formation of the nucleocapsid, we have expressed precore and core protein sequences in COS cells, a monkey kidney cell line, and compared the properties of these two particles. Our results show that core protein can form particles with various densities and they are present mostly in the cytosol. Precore protein, on the other hand, forms particles with one predominant density, and a majority of these particles are present in the lumen of the endoplasmic reticulum (ER). Furthermore, our results show that, when coexpressed in the same cells, core protein and the ER-associated surface antigens (envelope protein) show colocalization, indicating interaction between these two viral structural proteins.
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PMID:Comparative studies of hepatitis B virus precore and core particles. 240 5

The relationship between the presence of hepatitis B virus antigens, their localization and hepatitis B virus replication was studied in different clones of cultured HepG2 hepatoblastoma cells transfected with cloned hepatitis B virus DNA. Intracellular hepatitis B virus antigens were detected by immunofluorescence. The production of these antigens was evaluated in the culture media by enzyme-linked immunoassay. Hepatitis B virus DNA was detected using dot-blot hybridization. Three types of HBcAg staining were observed in transfected HepG2 cells: (a) cells with nuclear HBcAg, (b) cells with cytoplasmic HBcAg and (c) cells with both nuclear and cytoplasmic HBcAg. Cell types b and c also expressed hepatitis B virus DNA in their culture media. Our results suggest that cytoplasmic HBcAg may be more involved than nuclear HBcAg in hepatitis B virus replication. The site of hepatitis B virus formation in hepatocytes was studied by electron microscopic examination of a specific hepatitis B virus producer clone, thereby allowing detection of intracellular Dane particles more easily than liver biopsy samples from infected patients. Dane particles and HBsAg filaments were found in large, dilated structures probably related to the endoplasmic reticulum. Budding of core particles into cisternae of endoplasmic reticulum-related structures appears to be a possible mechanism for hepatitis B virus formation; our results suggest that the exocytosis of cisternae to extracellular spaces may be a mechanism for release of hepatitis B virus particles.
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PMID:Immunocytochemical and electron microscopic study of hepatitis B virus antigen and complete particle production in hepatitis B virus DNA transfected HepG2 cells. 240 29

The so-called novel inclusion body (NIB) is an intrahepatocytic structure which is frequently observed in human cirrhotic liver. It resembles very much to, but definitely differs from Hepatitis B surface antigen (HBsAg) morphologically. The age distribution of liver cirrhosis cases positive for NIB is similar to that positive for HBsAg, except for an existence of a time lag in mean age. One of the best staining methods to demonstrate NIB, for example, is to exhibit it as a reddish body stained by Luna, with a contrast of HBsAg counterstained purple in color by aldehyde fuchsin after thiosulfation. Electron microscopy of the liver obtained from a patient, negative for both HBsAg and Hepatitis B e antigen (HBeAg) but positive for Hepatitis B core antibody (HBcAb) and Hepatitis B surface antigen antibody (HBsAb) clinically, revealed some unfamiliar, tubular and cisternal arrays showing a network pattern and ring-shaped structure at the site exactly corresponding to NIB localization. These are considered to have been induced from the endoplasmic reticulum by an unknown agent, for which non A non B hepatitis virus (NANBV) is rationally postulated as one of the possibilities. A close relation between NIB and NANBV is highly suspected because of much similarities in histology, histochemistry, age distribution, and electron microscopy. The true nature of NANBV should be rescrutinized, especially in relation with Hepatitis B virus infection, since NIB is quite often observed also in cirrhotic liver positive for HBsAg.
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PMID:A study on so-called novel inclusion body in human hepatocyte. 241 47


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