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

Monoclonal hybridoma antibodies directed against the polypeptides of murine hepatitis virus-4 (JHM strain) were tested for their ability to alter the course of a normally lethal intracerebral virus challenge. Three monoclonal antibodies directed against two distinct epitopes on the E2 glycoprotein of MHV-4 protected mice against lethal virus challenge and converted the infection from fatal encephalomyelitis to demyelination. A single neutralizing antibody directed against a third epitope on E2 as well as seven nonneutralizing antibodies to E2, E1, and N polypeptides did not protect against challenge. In mice which received protective antibody, MHV-4 infection was not blocked, however, virus grew to lower titers in liver and brain, and virus replication in the CNS was more restricted than in unprotected mice. Decreased involvement of neurons in the brains of protected mice was observed, and no evidence of neuronal infection in the spinal cords was found. In contrast, oligodendrocytes were infected in the presence of protective antibody, and evidence of demylination associated with mononuclear cell infiltration was found. These studies demonstrate that antibody to a single epitope on a viral glycoprotein can substantially alter the course and phenotype of disease.
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PMID:Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. 619 89

Antisera prepared against each of three single and one pair of major structural proteins of the bovine coronavirus (Mebus strain) were used in immunoblotting studies to measure cross-reactivity with the structural proteins of the human coronavirus OC43 and the mouse hepatitis coronavirus A59. We conclude that the bovine coronavirus is comprised of four major structural proteins, gp190 (normally present as 120- and 100-kilodalton subunits), gp140, pp52, and gp26. The human coronavirus OC43 has an antigenically homologous counterpart of similar molecular mass to each of these proteins. The mouse hepatitis coronavirus A59 has an antigenically homologous counterpart to only three of these proteins: gp190, pp52 and gp26. There is no counterpart in the mouse virus to the 140-kilodalton glycoprotein, the apparent hemagglutinin of the bovine coronavirus.
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PMID:Antigenic relationships among proteins of bovine coronavirus, human respiratory coronavirus OC43, and mouse hepatitis coronavirus A59. 620 67

We have purified the seven virus-specific RNAs which were previously shown to be induced in Sac(-) cells upon infection with mouse hepatitis virus strain A59 (W. J. M. Spaan, P. J. M. Rottier, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 108:424-434, 1981). The individual RNAs, prepared by agarose gel electrophoresis of the polyadenylated RNA fraction from infected cells, were obtained pure, except for the preparations of RNAs 4, 5, and 6, which contained some contamination of RNA 7. The RNAs were microinjected into Xenopus laevis oocytes, and after incubation of these cells in the presence of [35S]methionine, the proteins synthesized were analyzed by polyacrylamide gel electrophoresis. Whereas no translation products of RNAs 1, 2, 4, and 5 were detected, the synthesis of virus-specific polypeptides coded by RNAs 3, 6, and 7 was observed. RNA 7 (0.6 X 10(6) daltons) directed the synthesis of a 54,000-molecular-weight polypeptide which comigrated with viral nucleocapsid protein and which was immunoprecipitated by antiserum from mice that had been infected with the virus. RNA 6 (0.9 X 10(6) daltons) directed the synthesis of three polypeptides with molecular weights of 24,000, 25,500, and 26,500, which migrated with the same electrophoretic mobilities as three low-molecular-weight virion polypeptides. After injection of RNA 3 (3.0 X 10(6) daltons), a polypeptide with a molecular weight of about 150,000 was immunoprecipitated. This polypeptide had no counterpart in the virion, but comigrated with a virus-specific glycoprotein present in infected cells which is immunoprecipitated by a rabbit antiserum against the mouse hepatitis virus strain A59 structural proteins. This antiserum could also immunoprecipitate the translation products of RNAs 3, 6, and 7. These results indicate that RNAs 3, 6, and 7 encode viral structural proteins. The significance of the data with respect to the strategy of coronavirus replication is discussed.
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PMID:Translation of three mouse hepatitis virus strain A59 subgenomic RNAs in Xenopus laevis oocytes. 626

The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.
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PMID:Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59. 632 91

alpha 1-Antitrypsin, the major serum protease inhibitor, is a glycoprotein synthesized in the liver. Severe deficiency results in protease-antiprotease imbalance, which predisposes to severe emphysema at a young age. Reduced serum levels reflect inadequate release of alpha 1-antitrypsin by the liver, which may be caused by specific defects in biosynthesis. The deficiency is inherited, with multiple codominant alleles at a single autosomal locus. Homozygous individuals, with severely reduced alpha 1-antitrypsin levels, have dyspnea, pulmonary function abnormalities, and respiratory disability from emphysema, usually in the fifth decade of life, with smokers being affected one decade earlier. Heterozygous individuals have intermediate alpha 1-antitrypsin levels and a more benign clinical course. Heterozygous smokers may have mild pulmonary function abnormalities, but these are of uncertain clinical significance. Hepatic involvement with transient neonatal hepatitis and cirrhosis with subsequent liver failure in adulthood represent the major extrapulmonary manifestations, occurring in 10% of homozygous individuals.
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PMID:alpha 1-Antitrypsin deficiency. 632 84

Two size classes of O-glycosidically linked oligosaccharides were liberated from glycoprotein E1 of mouse hepatitis virus (MHV) A59 by reductive beta-elimination and separated by h.p.l.c. The structures of the reduced oligosaccharides were determined by successive exoglycosidase digestions and by methylation analyses involving combined capillary gas chromatography-mass spectrometry and mass fragmentography after chemical ionization with ammonia. Oligosaccharide A (Neu5Ac alpha 2----3 Gal beta 1----3 GalNAc) comprised 35% of the total carbohydrate side chains, while the remaining 65% of the oligosaccharides of E1 had the branched structure B: Neu5Ac alpha 2----3 Gal beta 1----3 (Neu5Ac alpha 2----6) GalNAc. Both oligosaccharides were linked to the E1 polypeptide via N-acetylgalactosamine, and 20% of the sialic acids present in E1 glycopeptides were found to consist of N-acetyl-9-mono-O-acetylneuraminic acid. The reported structures of the O-linked glycans are discussed in the context of the amino acid sequence of E1, which exhibits a cluster of four hydroxyamino acids (Ser-Ser-Thr-Thr) as potential O-glycosylation sites at the amino terminus. Oligosaccharides with identical structures and an identical O-glycosylated tetrapeptide sequence are present in the blood group M-active glycophorin A of the human erythrocyte membrane.
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PMID:The carbohydrates of mouse hepatitis virus (MHV) A59: structures of the O-glycosidically linked oligosaccharides of glycoprotein E1. 632 80

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.
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PMID:Post-translational glycosylation of coronavirus glycoprotein E1: inhibition by monensin. 632 72

Uncertainties about the ultimate biologic consequences of using live virus vaccines to confer immunologic protection against CMV have focused attention on the use of noninfectious subunit vaccines. At least two classes of such preparations have been demonstrated to be effective in other systems. The first is virus particles bearing the relevant antigens but lacking nucleic acid (eg, hepatitis vaccine [31]). And the second class is biologically or chemically synthesized proteins or peptides with appropriate immunogenicity (eg, foot and mouth disease virus vaccine [32]). In this paper, two noninfectious CMV particles and several viral proteins have been discussed in view of their potential for use as such a vaccine. The two noninfectious virus particles discussed are referred to as dense bodies and NIEPs. The use of dense bodies for vaccine purposes has been suggested by others [14], but the simplicity of their composition has only recently been established [17]. Two characteristics of these particles make them attractive prospects for vaccine purposes. First, neither contains more than trace amounts of DNA or infectivity (ie, less than or equal to 0.1% that of virions). Thus, the concerns about possible adverse consequences of introducing DNA with the vaccine are greatly reduced. Second, both NIEPs and dense bodies contain all of the glycoprotein species present in virions and in approximately the same relative amounts. If, as anticipated, these proteins are important in eliciting the immune response to CMV, then NIEPs and dense bodies may be as effective as virions in that capacity. The fact that NIEPs contain the full complement of virion proteins, and in approximately the same relative amounts, suggests that they may produce a more complete immunologic response than dense bodies, which lack all of the capsid and most of the tegument proteins of the virion. Although NIEPs normally represent only a small percentage of the extracellular particles (eg, less than 1%), we have found that strain AD169 produces them in amounts nearly equivalent to virions. More importantly, we have shown here that NIEP production is essentially unaffected following treatment of infected cells with a concentration of hydroxyurea that reduced virion and dense body production by more than 90% (Fig. 6). Thus, by using strain AD169 to infect cells and hydroxyurea treatment for selective enrichment, it is possible to produce NIEPs in relatively large amounts and with theoretically very low levels of contaminating virions (ie, less than or equal to 0.01% infectivity of equivalent amount of virions).
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PMID:Selection of particles and proteins for use as human cytomegalovirus subunit vaccines. 632 69

The effect of the hepatoprotective drug silymarin (Carsil) on the incorporation rate of 14C-leucine into total proteins and on the biosynthesis of UDP-N-acetylhexosamine and microsomal glycoproteins using 14C-glucose of rat liver with D-galactosamine hepatitis was studied. It was found that i.p. treatment with Carsil in a dose of 140 mg/kg applied for 4 consecutive days partly abolishes the inhibitory effect of galactosamine on protein and glycoprotein biosynthesis. The specific activity of 14C-labelled UDP-N-acetylhexosamine is higher in the liver of D-galactosamine treated rats, compared with the specific activity of the nucleotide from liver pretreated with Carsil and then injected with galactosamine. This fact supports the suggestion that Carsil probably activates the metabolic conversion of UDP-hexosamine to the acetylated metabolite-UDP-N-acetylhexosamine, which is the normal liver cell metabolite, in liver cells.
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PMID:Effect of silymarin (Carsil) on the microsomal glycoprotein and protein biosynthesis in liver of rats with experimental galactosamine hepatitis. 688 84

CD8+ T cells with cytotoxic activity against the surface glycoprotein (S) of mouse hepatitis virus, strain JHM, have been identified in the central nervous system (CNS) of both acutely and chronically infected C57BL/6 mice. In this report, two specific epitopes recognized by these CNS-derived cells were identified, using a panel of peptides chosen because they conformed to the allele-specific binding motif for MHC class I H-2Kb and H-2Db. The active peptides encompassed residues 510 to 518 (CSLWNGPHL, H-2Db) and 598 to 605 (RCQIFANI, H-2Kb). Both epitopes are located within the region of the S protein previously shown to be prone to deletion after passage in animals. These deleted strains are generally less neurovirulent than the wild-type virus but still are able to cause demyelination. Since C57BL/6 mice become persistently infected more commonly than many other strains of mice, these data are consistent with a role for CD8+ T-cell escape mutants in the pathogenesis of the demyelinating disease. This is the first report of CD8+ T-cell epitope localization within the S protein, the protein most strongly implicated thus far in pathogenesis in the host.
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PMID:CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity. 749 35


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