Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure is described that allows the characterization of the molecular forms of beta-hexosaminidase and cathepsin D in controls and pathological specimens of human serum and human urine. The following observations were made. (1) In human serum, beta-hexosaminidase (alpha- and beta-chain) and cathepsin D are present predominantly in their high-molecular-weight precursor forms. In human urine, these enzymes exist as both precursor and mature forms. (2) Cathepsin D precursor from serum and urine differs in the number of oligosaccharides that are sensitive to endo-beta-N-acetylglucosaminidase H. Therefore the urine enzyme is not likely to originate from the serum. (3) The presence exclusively of precursors of beta-hexosaminidase and of cathepsin D in the sera of patients with hepatitis suggests that in hepatitis secretion of lysosomal enzymes is elevated, rather than the enzymes leaking from damaged cells. (4) In the urine of patients with nephrotic syndrome, beta-hexosaminidase and cathepsin D are present in grossly elevated amounts, but do not differ in the polypeptide patterns from controls. (5) In urine from a patient with mucolipidosis II, the elevated activity of beta-hexosaminidase is accounted for mainly by the precursor forms. Mature beta-chain of beta-hexosaminidase is lacking, and incompletely processed beta-hexosaminidase polypeptides are present. Both the precursor and the mature forms of cathepsin D are increased. They contain only complex oligosaccharides.
 ...
PMID:Molecular forms of beta-hexosaminidase and cathepsin D in serum and urine of healthy subjects and patients with elevated activity of lysosomal enzymes. 622 25

The intracellular sites of biosynthesis of the structural proteins of murine hepatitis virus A59 have been analyzed using cell fractionation techniques. The nucleocapsid protein N is synthesized on free polysomes, whereas the envelope glycoproteins E1 and E2 are translated on the rough endoplasmic reticulum (RER). Glycoprotein E2 present in the RER contains N-glycosidically linked oligosaccharides of the mannose-rich type, supporting the concept that glycosylation of this protein is initiated at the co-translational level. In contrast, O-glycosylation of E1 occurs after transfer of the protein to smooth intracellular membranes. Monensin does not interfere with virus budding from the membranes of the endoplasmic reticulum, but it inhibits virus release and fusion of infected cells. The oligosaccharide side chains of E2 obtained under these conditions are resistant to endoglycosidase H and lack fucose suggesting that transport of this glycoprotein is inhibited between the trans Golgi cisternae and the cell surface. Glycoprotein E1 synthesized in the presence of monensin is completely carbohydrate-free. This observation suggests that the intracellular transport of this glycoprotein is also blocked by monensin.
 ...
PMID:Post-translational glycosylation of coronavirus glycoprotein E1: inhibition by monensin. 632 72

The intracellular interaction of the coronavirus mouse hepatitis virus (MHV) with its cellular receptor (MHVR) was investigated. Overexpression of MHVR from vaccinia vectors during an ongoing MHV infection resulted in dramatic inhibition of virus production. Infectivity in both cytoplasmic extracts and supernatants was reduced by over three orders of magnitude relative to control cultures in which a truncated MHVR lacking virus binding activity was expressed. Complete MHV virions were not detectable in supernatants of MHVR expressing cells. In the presence of overexpressed MHVR, the coronavirus spike protein was not cleaved into posttranslation products S1 and S2, nor was it fully processed into a form resistant to endoglycosidase H digestion, indicating that intracellular engagement of spike with receptor prevented spike transport and consequent association with virions.
 ...
PMID:Overexpression of the MHV receptor. Effect on progeny virus secretion. 883 May 3

Two temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59, ts43 and ts379, have been described previously to be ts in infectivity but unaffected in RNA synthesis (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). We present a detailed analysis of the protein synthesis of the mutant viruses at the permissive (31 degrees C) and nonpermissive (39.5 degrees C) temperatures. It was found that synthesis of the nucleocapsid protein N and the membrane protein M of both viruses was insensitive to temperature. However, the surface protein S of both viruses was retained in the endoplasmic reticulum at the nonpermissive temperature. This was shown first by analysis of endoglycosidase H-treated and immunoprecipitated labeled S proteins. The mature Golgi form of S was not present at the nonpermissive temperature for the ts viruses, in contrast to wild-type (wt) virus. Second, gradient purification of immunoprecipitated S after pulse-chase labeling showed that only wt virus S was oligomerized. We conclude that the lack of oligomerization causes the retention of the ts S proteins in the endoplasmic reticulum. As a result, ts virus particles that were devoid of S were produced at the nonpermissive temperature. This result could be confirmed by biochemical analysis of purified virus particles and by electron microscopy.
 ...
PMID:Characterization of two temperature-sensitive mutants of coronavirus mouse hepatitis virus strain A59 with maturation defects in the spike protein. 899 12

Patients with primary biliary cirrhosis (PBC) frequently produce autoantibodies against gp210, an integral glycoprotein of the nuclear pores. this protein consists of three main domains: a large glycosylated lumenal domain, a single hydrophobic transmembrane segment and a short cytoplasmic tail. It has been previously shown that autoantibodies from PBC patients exclusively react with the cytoplasmic tail when recombinant rat gp210 expressed in Escherichia coli was used as antigen. Using human gp210 isolated from HeLa cells we found the lumenal domain as the major target. The aim of this study was to further characterize the dominant autoepitopes of gp210. Sera from 88 patients with autoimmune liver disease and 20 controls were used. Gp210 protein was digested with papain or endoglycosidase H and then subjected to immunoblotting. Autoantibodies against gp210 were detected in 12 of 43 (28%) PBC patients, but in none of the autoimmune hepatitis and control sera. Four of 12 (33%) anti-gp210 positive sera reacted with a fragment consisting of the cytoplasmic tail and 8 (66%) sera targeted an epitope located within the large lumenal domain. Furthermore, our data show that antigenic determinant is restricted to the 64 kD glycosylated amino-terminal fragment and that carbohydrate residues are an essential part of this novel epitope. We suggest that antigens possessing both epitopes namely; the glycosylated lumenal domain and the cytoplasmic tail should be used for screening tests in order to detect all sera with anti-gp210 specificity.
 ...
PMID:Anti-gp210 antibodies in sera of patients with primary biliary cirrhosis. Identification of a 64 kD fragment of gp210 as a major epitope. 914 Jul 28

The coronavirus nonstructural proteins (nsp's) derived from the replicase polyproteins collectively constitute the viral replication complexes, which are anchored to double-membrane vesicles. Little is known about the biogenesis of these complexes, the membrane anchoring of which is probably mediated by nsp3, nsp4, and nsp6, as they contain several putative transmembrane domains. As a first step to getting more insight into the formation of the coronavirus replication complex, the membrane topology, processing, and subcellular localization of nsp4 of the mouse hepatitis virus (MHV) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were elucidated in this study. Both nsp4 proteins became N glycosylated, while their amino and carboxy termini were localized to the cytoplasm. These observations imply nsp4 to assemble in the membrane as a tetraspanning transmembrane protein with a Nendo/Cendo topology. The amino terminus of SARS-CoV nsp4, but not that of MHV nsp4, was shown to be (partially) processed by signal peptidase. nsp4 localized to the endoplasmic reticulum (ER) when expressed alone but was recruited to the replication complexes in infected cells. nsp4 present in these complexes did not colocalize with markers of the ER or Golgi apparatus, while the susceptibility of its sugars to endoglycosidase H indicated that the protein had also not traveled trough the latter compartment. The important role of the early secretory pathway in formation of the replication complexes was also demonstrated by the inhibition of coronaviral replication when the ER export machinery was blocked by use of the kinase inhibitor H89 or by expression of a mutant, Sar1[H79G].
 ...
PMID:Localization and membrane topology of coronavirus nonstructural protein 4: involvement of the early secretory pathway in replication. 1785 19