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)

Our recent studies suggested that neurons and epithelial cells sort viral glycoproteins in a similar manner. The apical influenza virus haemagglutinin was preferentially delivered to the axon of hippocampal neurons in culture, whereas the basolateral vesicular stomatitis virus glycoprotein was sorted to the dendrites. To investigate whether other membrane proteins showed similar sorting in neurons and epithelial cells, we have analysed the localization of a glypiated (glycosylphosphatidylinositol anchored) protein, Thy-1, in hippocampal neurons in culture. In MDCK and other epithelial cells, endogenous glycosylphosphatidylinositol (GPI)-anchored proteins, as well as mutated exogenous proteins containing the GPI-attachment signal, undergo preferential delivery to the apical surface. This polarized sorting of GPI-anchored proteins has been proposed to occur by the same mechanisms as the sorting of glycolipids to the apical surface. We report here that the neuronal GPI-protein Thy-1 is present in hippocampal neurons in culture and is exclusively located on the axonal surface. This finding further strengthens our hypothesis that the mechanisms of sorting of surface components may be similar in neurons and epithelial cells.
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PMID:Polarized sorting of glypiated proteins in hippocampal neurons. 167 Aug 98

The vesicular stomatitis virus glycoprotein forms noncovalently linked trimers in the endoplasmic reticulum before being transported to the Golgi apparatus. The experiments reported here were designed to determine if the extracellular domain of the glycoprotein contains structural information sufficient to direct trimer formation. To accomplish this, we generated a construct encoding G protein with the normal transmembrane and anchor sequences replaced with the sequence encoding 53 C-terminal amino acids from the Thy-1.1 glycoprotein. We show here that these sequences were able to specify glycolipid addition to the truncated G protein, probably after cleavage of 31 amino acids derived from Thy-1.1. The glycolipid-anchored G protein formed trimers and was expressed on the cell surface in a form that could be cleaved by phosphoinositol-specific phospholipase C. However, the rate of transport was reduced, compared with that of wild-type G protein. A second form of the G protein was generated by deletion of only the transmembrane and cytoplasmic domains. This mutant protein also formed trimers with relatively high efficiency and was secreted slowly from cells.
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PMID:Oligomerization of glycolipid-anchored and soluble forms of the vesicular stomatitis virus glycoprotein. 255 57

We have been studying delayed hypersensitivity (DH) to herpes simplex virus (HSV) in order to examine the role of this response in host defense against acute and recurrent HSV infections. In previous reports the basic parameters of DH to HSV have been characterized by using a murine ear swelling model, and also the regulation of DH to HSV induced by i.v. injection of the virus. In this paper, we describe a murine protection system and our use of the ability to specifically regulate DH to HSV to examine the correlation between T cells that transfer DH (TDH) and cells that transfer protection from acute HSV infection. Both DH and protection can be transferred with lymph node cells from mice immunized subcutaneously 4 days previously. The effector cell appears to be a T cell, because serum from these donors confers no protection and treatment of immune cells with anti-Thy-1.2 plus complement reduced their ability to protect. Tolerance of DH to HSV was induced by i.v. injection 7 days before subcutaneous immunization. Tolerized mice were unable to generate protective cells. Furthermore, tolerized mice contained suppressor T cells that suppressed not only DH but also the development of protective cells. Regulation of protective cells was shown to be virus specific, because mice tolerized with vesicular stomatitis virus (VSV) were not impaired in their ability to generate T cells that protected from HSV infection. The correlation between the TDH cell and cells that transfer protection from acute HSV infection is discussed.
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PMID:Delayed hypersensitivity and immune protection against herpes simplex virus: suppressor T cells that regulate the induction of delayed hypersensitivity effector T cells also regulate the induction of protective T cells. 258 6

Using the indirect immunoelectron microscopy technique, it was investigated whether during assembly of murine leukaemia virus (MuLV) and vesicular stomatitis virus (VSV), the glycoproteins (gp) Thy-1, H-2, Pgp-1 and T-200 present on the surface of BW5147 and BuEL4 leukaemia cell lines were incorporated into the virus envelopes. This work was done mainly with monoclonal antibodies against these gps to exclude the presence of antibodies against endogenous MuLV present in conventional mouse antisera. Thy-1 gps were incorporated into MuLV and VSV envelopes. In contrast, H-2, Pgp-1 and T-200 gps were excluded from the budding of both virus particles. To study whether the presence of Thy-1 gps on the viral envelopes is due to some lateral affinity of this molecule with viral gps, the physical association of Thy-1.1 antigens and MuLV antigens was studied with antibody-induced redistribution of both antigens on the BW5147 cell surface. Antibody-induced patching of the viral antigens did not result in co-patching of the Thy-1.1 antigens. In the reciprocal tests no co-redistribution of viral antigens with Thy-1.1 antigens was seen. These studies show that the presence of Thy-1.1 gp on the MuLV envelope cannot be due to a lateral affinity of this molecule with viral gps and that a selection of surface gps takes place during assembly of MuLV and VSV.
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PMID:Specific selection of host cell glycoproteins during assembly of murine leukaemia virus and vesicular stomatitis virus: presence of Thy-1 glycoprotein and absence of H-2, Pgp-1 and T-200 glycoproteins on the envelopes of these virus particles. 613 9

When mouse lymphoid cells derived from untreated C57BL/6 mice were cocultivated in liquid cultures with L-cell monolayers for 3 h, overlaid with soft agar, and then further incubated for 12 h, protected foci of L cells against vesicular stomatitis virus infection were formed. Many strains of mice have been found to have the protected focus-forming cells on the L-cell monolayers. The formation of the protected foci was completely suppressed by addition of cycloheximide into soft agar. When anti-interferon (type I) antiserum was added to soft agar, there was a decrease in focus counts of about 80%. These experimental results indicated that the formation of protected foci by untreated mouse lymphoid cells was mediated for the most part by type I interferon that was produced without addition of special inducer. We have designated these focus-forming cells as natural interferon-producing cells (NIPC). NIPC belong to the glass-adherent fraction, and Thy-1 antigen, immunoglobulin, and Ia antigen could not be detected on the surface of the NIPC. NIPC were detected in congenitally athymic nude mice. These findings suggest that NIPC belong to the Ia-negative macrophages. Mouse lymphoid cells obtained from germfree mice could form the protected foci on L-cell monolayers and could produce interferon without the addition of a special inducer. NIPC are considered to be a cellular background for spontaneous interferon production.
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PMID:Natural interferon-producing cells in mice. 616 18

Cytotoxic T lymphocytes (CTL) generated in mice against a particular serotype of vesicular stomatitis virus (VSV) were previously shown to cross-reactively lyse syngeneic target cells infected with serologically distinct types of VSV. To analyze the antigenic basis of this T cell cross-reactivity, we generated CTL against VSV-Indiana (VSV-Ind) and established them by limiting dilution as cloned in vitro cell lines. The cells continuously proliferate in medium containing concanavalin A-induced T cell growth factors. All of the cells are Thy-1.2+ and Lyt-2.2+. Lysis by these cells is H-2Dd-restricted, no natural killer cell activity is detectable, and all the clones cross-reactively lyse target cells infected with either VSV-Ind or VSV-New Jersey (VSV-NJ). In addition, no specific blocking of primary, secondary, or cloned anti-VSV CTL was achieved with the use of several monoclonal antibodies specific for the glycoprotein of VSV and capable of neutralizing either VSV-Ind or VSV-NJ. These results suggest that VSV serotype-specific neutralizing antibodies may recognize immunodominant determinants of VSV glycoprotein that are distinct from those recognized by the majority of VSV-specific CTL.
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PMID:Specificity of in vitro cytotoxic T cell clones directed against vesicular stomatitis virus. 619 Sep 24

The envelope glycoprotein, G, of vesicular stomatitis virus (VSV) is initially glycosylated by the en bloc transfer of Glc3Man9GlcNAc2 oligosaccharides to 2 specific asparagine residues in the nascent polypeptide chain. We carried out in vivo and in vitro studies to determine whether the size of the oligosaccharide chains on two related but different G proteins can affect their ability to fold correctly. For the in vivo studies we used a mutant lymphoma cell line, Thy-1-e, which transfers the truncated oligosaccharide, Glc3Man5GlcNAc2, to nascent polypeptides. The growth of VSV in these cells was temperature-sensitive compared to that in parental Thy-1+ cells, and VSV (San Juan) was more affected than VSV (Orsay). These results are congruous with our previous observation that in the absence of glycosylation virus assembly is temperature-sensitive and VSV (San Juan) is inhibited more than VSV (Orsay). To examine the effect of oligosaccharide size on the properties of the G protein in vitro we treated G proteins containing either Man8GlcNAc2 or Man5GlcNAc2 oligosaccharide chains with guanidine hydrochloride and measured their ability to refold using an in vitro aggregation assay. The San Juan G protein with Man5GlcNAc2 oligosaccharides aggregated at 40 degrees C but not at 30 degrees C. The Orsay G protein with Man5GlcNAc2 oligosaccharides and both proteins containing Man8GlcNAc2 oligosaccharides did not aggregate at either temperature. We conclude that the size of the oligosaccharides present on the folding G protein can be crucial in attaining a proper conformation, and the extent of their effect depends on the primary structure of the polypeptide.
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PMID:The effect of oligosaccharide chains of different sizes on the maturation and physical properties of the G protein of vesicular stomatitis virus. 625 53

Fetal hippocampal neurons develop axons and dendrites in culture. To study how neurons form and maintain different plasma membrane domains, hippocampal neurons were infected with RNA viruses and the distribution of the viral glycoproteins was analyzed by light and electron microscopy. Infection of hippocampal cells with vesicular stomatitis virus (VSV) and fowl plague virus (FPV) resulted in the polarized distribution of the newly synthesized viral glycoproteins. The VSV glycoprotein appeared firstly in the Golgi apparatus and then in the dendrites. In contrast, the hemagglutinin of FPV, after accumulation in the Golgi apparatus, moved to the axons. These results suggest that the mechanism of sorting of viral glycoproteins might be similar in neurons and MDCK cells, a cell line of epithelial origin. In these cells the VSV glycoprotein and the hemagglutinin of FPV distribute to the basolateral and apical membranes, respectively. Transport of viral glycoproteins to both neuronal domains was microtubule dependent. Nocodazole treatment of infected neurons inhibited the delivery of axonal and dendritic viral glycoproteins equally. To investigate if the analogy between epithelial cells and neurons extended to include an endogenous plasma membrane protein, the distribution of Thy-1, a GPI-linked protein, was analyzed. By immunofluorescence and immunoelectron microscopy, Thy-1 was found exclusively along the axonal surface. In epithelial cells GPI-anchored proteins are located apically. The existence of a barrier on the neuronal plasma membrane that would prevent intermixing of axonal and dendritic proteins was analyzed by a liposomefusion assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Membrane traffic in polarized neurons in culture. 814 7

Gene therapy strategies for humans have been limited by low transduction efficiencies and poor expression of retroviral vectors in differentiated progeny cells carrying the transduced vector. Here we describe a strategy utilizing a cell surface reporter gene, murine thy-1.2, selectable by fluorescence-activated cell sorting (FACS), to achieve higher gene marking efficiencies. Human CD34-positive cells were transduced by a murine retroviral vector bearing the thy-1.2 marker and pseudotyped with vesicular stomatitis virus G protein, followed by FACS to enrich for CD34-positive cells that express Thy-1.2 on the cell surface. Gene marking and expression after differentiation into thymocytes were assessed in a SCID-hu Thy/Liv mouse model for human lymphoid progenitor cell gene therapy. We found that virtually all of the differentiated T-cell progeny were marked with vector sequences. It is of particular importance that reconstitution with the selected cells resulted in expression of Thy-1.2 in up to 71% of donor-derived thymocytes. It is of note that the donor-derived thymocytes that did not express Thy-1.2 still harbored vector thy-1.2 sequences, suggesting repression of transgene expression in some cells during progenitor cell differentiation into thymocytes. These studies provide a proof of concept for efficient expression of transgenes through T-lymphoid differentiation and a potential basis for utilizing similar strategies in human gene therapy clinical trials.
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PMID:High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells. 899 65