Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the particular intracellular steps in the glycosylation of the vesicular stomatitis virus (VSV) glycoprotein that were altered in several lectin-resistant CHO cell lines, VSV-infected parental and mutant cells were pulse-labeled for 30 and 120 min with [3H]mannose and [3H]glucosamine. Cell-associated viral glycopeptides were analyzed by gel filtration combined with specific glycosidase digestions and compared with the corresponding mature virion oligosaccharides. The intracellular glycosylation of the VSV glycoprotein in a mutant cell line resistant to phytohemagglutinin was identical to that in the normal cells except for a complete block in processing at a specific step in the final trimming of the oligomannosyl core from five to three mannoses. The results demonstrated that a double-mutant cell line selected from the phytohemagglutinin-resistant cells for resistance to concanavalin A had an additional defect in one of the earliest stages of glycosylation, resulting in smaller precursor oligosaccharides linked to protein.
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PMID:Altered synthesis and processing of oligosaccharides of vesicular stomatitis virus glycoprotein in different lectin-resistant Chinese hamster ovary cell lines. 625 77

Autoradiography of colony replicas immobilized on filter paper was used to isolate a Chinese hamster ovary cell line deficient in incorporation of radiolabeled fucose into a trichloroacetic acid-insoluble fraction. This cell line, called 62.1, has the same growth rate at 37 degrees C as wild-type cells, but incorporates five times less fucose into acid-insoluble radioactivity. Chemical analysis of fucose bound to macromolecules also showed a fivefold reduction in the mutant. The fucoproteins of the mutant cell line differ qualitatively from those of wild-type cells as visualized by SDS gel electrophoresis fluorography; no differences were detected between total proteins as visualized by coomassie blue staining. The macromolecular sialic acid content of the mutant was somewhat higher than the wild type (20%). Studies of the synthesis of the glycoprotein of vesicular stomatitis virus in mutant and wild-type cells showed that the mutant is unable to synthesize complex-type N-linked oligosaccharides. Enzyme assays show that ths defect in the mutant is due to reduction in UDP-N-acetylglucosamine-glycoprotein N-acetyl-glucosaminyltransferase, a key enzyme in the assembly of complex glycopeptides. Hybridization studies have shown that mutant 62.1 has common mutations belonging to the same complementation group as mutant PhaR1-1. This latter mutant was previously isolated using lectin resistance by Stanley et al. (1975) and was also deficient in the above N-acetyl-glucosaminyltransferase.
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PMID:Autoradiographic detection and characterization of a Chinese hamster ovary cell mutant deficient in fucoproteins. 628 69

The asparagine-linked oligosaccharides of the G protein of the Hazelhurst subtype of the New Jersey serotype of vesicular stomatitis virus (VSV) have been compared with the oligosaccharides from the G protein of the well-characterized Indiana serotype of VSV, with baby hamster kidney cells in monolayer culture as the host for both viruses. [3H]Glucosamine- and [3H]mannose-labeled glycopeptides from the G protein of purified virus were analyzed by the combined techniques of endo-beta-N-acetylglucosaminidase H (ENDO-H) digestion, concanavalin A and lentil lectin affinity chromatography, and Bio-Gel P-4 chromatography. Although almost all of the Indiana G protein oligosaccharides were acidic-type structures, as expected from previous studies; the Hazelhurst G protein contained a mixture of acidic-type, hybrid-type containing sialic acid, and neutral-type (predominantly Man5-6GlcNAc2-Asn) structures. The vast majority of acidic-type oligosaccharides from both the Hazelhurst and Indiana G proteins were diantennary structures, with less than half containing fucose linked to the innermost N-acetylglucosamine. Additional analysis of the Hazelhurst G protein by ENDO-H digestion and gel electrophoresis suggested that some of the mature G polypeptides contained acidic-type structures at both glycosylation sites, whereas the remainder contained an ENDO-H-resistant, acidic-type structure at one site and an ENDO-H-sensitive, hybrid- or neutral-type structure at the other site.
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PMID:Unusual heterogeneity in the glycosylation of the G protein of the hazelhurst strain of vesicular stomatitis virus. 631 2

Carbohydrate moieties derived from the G glycoprotein of Vesicular Stomatitis Virus (VSV) grown in parental Chinese hamster ovary (CHO) cells and the glycosylation mutant Lec4 have been analyzed by high-field 1H NMR spectroscopy. The major glycopeptides of CHO/VSV and Lec4/VSV were purified by their ability to bind to concanavalin A-Sepharose. The carbohydrates in this fraction are of the biantennary, complex type with heterogeneity in the presence of alpha(2,3)-linked sialic acid and alpha (1,6)-linked fucose residues. A minor CHO/VSV glycopeptide fraction, which does not bind to concanavalin A-Sepharose but which binds to pea lectin-agarose, was also investigated by 1H NMR spectroscopy. These carbohydrates are complex moieties which appear to contain N-acetylglucosamine in beta(1,6) linkage. Their spectral properties are most similar to those of a triantennary complex oligosaccharide containing a 2, 6-disubstituted mannose alpha (1,6) residue. Carbohydrates of this type are not found among the glycopeptides of VSV grown in the Lec4 CHO glycosylation mutant.
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PMID:1H NMR spectroscopy of carbohydrates from the G glycoprotein of vesicular stomatitis virus grown in parental and Lec4 Chinese hamster ovary cells. 632 83

Independently derived mutants of Chinese hamster ovary cells have been isolated and shown to exhibit a subtle glycosylation defect resulting in the premature termination of certain asparagine-linked carbohydrate moieties. This carbohydrate alteration is akin to the types of structural variation termed microheterogeneity and is thought not to affect the biological activities of glycoproteins that manifest the phenomenon. However, the carbohydrate change expressed by the mutants is stable and heritable, and 125I-lectin-binding studies suggest that it profoundly alters their surface recognition properties. The mutation appears to affect a specific subpopulation of galactose residues in asparagine-linked carbohydrate of the type found associated with the G glycoprotein of vesicular stomatitis virus. The mutant cells also exhibit morphological changes in substratum culture.
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PMID:Microheterogeneity among carbohydrate structures at the cell surface may be important in recognition phenomena. 719 40

Peripheral blood dendritic cells (DC) produce IFN-alpha in response to challenge by many enveloped viruses including herpes simplex virus (HSV) and HIV, whereas Sendai virus predominantly stimulates IFN-alpha production by monocytes. Glycosylated viral envelope proteins are known to be important for the induction of IFN-alpha. In this study we demonstrate that stimulation of IFN-alpha synthesis by HSV is inhibited by a number of monosaccharides, including fucose, N-acetylglucosamine, and N-acetylgalactosamine as well as the yeast polysaccharide mannan, supporting a role for lectin(s) in the IFN-alpha stimulation pathway. Furthermore, antiserum to the mannose receptor (MR) also inhibited HSV, vesicular stomatitis virus, and HIV-induced IFN-alpha production, but failed to inhibit the IFN-alpha induced by Sendai virus. We further demonstrated that freshly isolated blood DC and IFN-alpha-producing cells responding to HSV stimulation express the MR. This study therefore implicates the MR as an important receptor for the nonspecific recognition of enveloped viruses by DC and the subsequent stimulation of IFN-alpha production by these viruses. Thus, the MR probably serves as a critical link between innate and adaptive immunity to viruses, especially given the role of the MR in Ag capture by DC and the importance of IFN-alpha in shaping immunity.
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PMID:The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses. 972 35

To analyze the role of glucose trimming and reglucosylation in the binding of substrate proteins to calnexin in the endoplasmic reticulum (ER) of living cells, we made use of the thermosensitive vesicular stomatitis virus tsO45 glycoprotein (G protein). At nonpermissive temperature the G protein failed to fold completely and remained bound to calnexin. When the cells were shifted to permissive temperature, complete folding occurred accompanied by glucosidase-mediated elimination of calnexin-G protein complexes. If release from calnexin was blocked during the temperature shift by inhibiting the glucosidases, folding occurred, albeit at a reduced rate. In contrast, when unfolded by a shift from permissive to nonpermissive temperature, the G protein was reglucosylated rapidly and became capable of rebinding to calnexin. The rate at which calnexin binding occurred showed a 20-min delay that was explained by accumulation of the G protein in calnexin-free exit sites of the ER. These contained the glucosyltransferase responsible for reglucosylation of misfolded glycoproteins but had little or no calnexin. After unfolding and reglucosylation, the G proteins moved slowly from these structures back to the ER where they reassociated with the chaperone. Taken together, these results in live cells fully supported the lectin-only model of calnexin function. The ER exit sites emerged as a potentially important location for components of the quality control system.
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PMID:Trimming and readdition of glucose to N-linked oligosaccharides determines calnexin association of a substrate glycoprotein in living cells. 1006 21

We have previously reported the generation of pseudotype virus from chimeric gene constructs encoding the ectodomain of the E1 or E2 glycoprotein of hepatitis C virus (HCV) genotype 1a appended to the trans membrane domain and cytoplasmic tail of the vesicular stomatitis virus (VSV) G protein. Sera derived from chimpanzees immunized with homologous HCV glycoproteins neutralized pseudotype virus infectivity (L. M. Lagging et al., J. Virol. 72, 3539-3546, 1998). We have now extended this study to further understand the role of HCV glycoproteins in pseudotype virus entry. Although a number of mammalian epithelial cells were susceptible to VSV/HCV pseudotype virus infection, plaquing efficiency was different among host cell lines. Pseudotype virus adsorption at low temperature decreased plaque numbers. Treatment of E1 or E2 pseudotype virus in media between pH 5 and 8 before adsorption on cells did not significantly reduce plaque numbers. On the other hand, treatment of cells with lysosomotropic agents or inhibitors of vacuolar H(+) ATPases had an inhibitory role on virus entry. Concanavalin A, a plant lectin, exhibited neutralization of both HCV E1 and E2 pseudotype virus infectivity. However, mannose binding protein, a C-type mammalian lectin, did not neutralize virus in the absence or presence of serum complement. Pseudotype virus infectivity was only partially inhibited by heparin, a highly sulfated glycosaminoglycan, in a saturable manner. Additional studies suggested that low-density lipoprotein receptor related molecules partially inhibit E1 pseudotype virus infectivity, while CD81 related molecules interfere with E2 pseudotype virus infectivity. A further understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection.
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PMID:Functional features of hepatitis C virus glycoproteins for pseudotype virus entry into mammalian cells. 1102 9

Viral infections are often accompanied by extensive proliferation of reactive CD8 T cells. After a defined number of divisions, normal somatic cells enter a nonreplicative stage termed senescence. In the present study we have identified the inhibitory killer cell lectin-like receptor G1 (KLRG1) as a unique marker for replicative senescence of murine CD8 T cells. KLRG1 expression was induced in a substantial portion (30-60%) of CD8 T cells in C57BL/6 mice infected with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus, or vaccinia virus. Similarly, KLRG1 was found on a large fraction of LCMV gp33 peptide-specific TCR-transgenic (tg) effector and memory cells activated in vivo using an adoptive transfer model. Transfer experiments with CFSE-labeled TCR-tg cells into LCMV-infected hosts further indicated that induction of KLRG1 expression required an extensive number of cell divisions. Most importantly, KLRG1(+) TCR-tg effector/memory cells could efficiently lyse target cells and secrete cytokines, but were severely impaired in their ability to proliferate after Ag stimulation. Thus, this study demonstrates that senescent CD8 T cells are induced in abundant numbers during viral infections in vivo.
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PMID:Viral infections induce abundant numbers of senescent CD8 T cells. 1167 87

The complement system is a critical component of both the innate and acquired immune systems. It is important in host defense against viruses, bacteria, and fungi for opsonization and for lysis of pathogens. However, activated complement can also cause tissue damage. There is compelling evidence that complement factors are presented in the central nervous system (CNS). Complement activation (by any of the three pathways: classical, alternate, and lectin) can lead to inflammation and tissue damage, while at the same time may also restrict certain pathogens in the CNS. C5a is formed by proteolytic cleavage C5. C5a is considered the most potent proinflammatory mediator, often called an anaphylotoxin. In this communication, we examine the roles of C5 (C5a) in vesicular stomatitis virus (VSV)-induced encephalitis. We found that C5a is produced during VSV infection, but C5-deficient mice had similar pathology as their controls. We concluded that C5 is not a critical factor in mediating the host response during VSV encephalitis.
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PMID:Innate immunity in viral encephalitis: role of C5. 1208 Oct 18


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