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)

Cytopathic changes and virus-specific antigens developed in, then disappeared from, mouse fibroblasts infected by a strain of human cytomegalovirus (CMV), but their disappearance was delayed in cells treated with idoxuridine prior to infection. The replication of vesicular stomatitis virus and herpes simplex virus was restricted in human CMV-infected mouse cells as long as human CMV-specific antigens were present. Virus-specific antigens could be induced by treatment with idoxuridine or arginine deficiency in mouse cells which had previously turned "negative".
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PMID:Virus-specific changes in mouse cells inoculated with a strain of human cytomegalovirus. 16 41

This study describes an analysis of the interaction of individual amino acid residues of the vesicular stomatitis virus (VSV) nucleocapsid antigenic octapeptide (N52-59; Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu) with the H-2Kb molecule and T-cell receptors (TCRs). Tyr-3, Tyr-5, and Leu-8 were the positions in the peptide found to be H-2Kb contact residues by analyzing single alanine-substituted peptides in a competition assay with a Kb-restricted antigenic nonapeptide of Sendai virus. Arg-1, Gly-2, Val-4, Gln-6, and Gly-7 of the peptide were identified as putative TCR contact residues by testing the peptide analogs for their capacity to sensitize targets for VSV-specific cytolytic T-lymphocyte clones. The octamer N52-59 was the optimal length of the peptide required for binding to Kb. This peptide length requirement and the finding of an irregular interspersing of major histocompatibility complex and TCR contact residues are most consistent with the conclusion that the peptide is in an extended conformation in the antigen binding groove. Furthermore, data on binding of truncated peptides show that, although the Arg-1 side chain has been assigned as a TCR contact residue, the main-chain atoms of the N-terminal amino group are most likely involved in interacting with the major histocompatibility complex molecule. A panel of H-2Kb point mutants was constructed to explore the effect of altered amino acid residues on the binding of N52-59. Mutants with amino acid substitutions along the floor of the groove all bound the VSV peptide but modulated its interaction with Kb, apparently causing subtle changes in the spatial arrangement of some specific TCR contact residues in the peptide.
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PMID:Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus. 131 83

Cells respond to treatment with interferons by synthesizing several induced proteins, including one or more structurally related proteins collectively called Mx. Nuclear and cytoplasmic forms of Mx have been described, some of which inhibit virus replication. Human MxA is a cytoplasmic protein that specifically inhibits the multiplication of influenza virus and vesicular stomatitis virus. Here, we describe a mutant MxA protein, MxA(R645), which inhibited influenza virus but was inactive against vesicular stomatitis virus. It differs from wild-type MxA by a Glu to Arg substitution near the carboxy terminus. Like wild-type MxA, and as expected for an Mx protein acting in the cytoplasm, MxA(R645) blocked influenza virus at a step after primary transcription. When moved to the nucleus of transfected cells with the help of a foreign nuclear transport signal, its mode of action changed. Like mouse Mx1, nuclear MxA(R645) interfered with primary transcription of influenza virus, which is a nuclear process. Our results thus define an MxA region that determines antiviral specificity and further demonstrate that nuclear forms of MxA can mimic the action of mouse Mx1 whose natural location is the cell nucleus.
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PMID:Mechanism of human MxA protein action: variants with changed antiviral properties. 131 72

To study the structure of a homogenous major histocompatibility complex (MHC) class I molecule containing a single bound peptide, a complex of recombinant mouse H-2Kb, beta 2-microglobulin (beta 2m), and a fragment of the vesicular stomatitis virus (VSV) nuclear capsid protein, VSV-(N52-59) octapeptide (Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu), was prepared by exploiting a high-yield bacterial expression system and in vitro cocomplex formation. The structure of mouse H-2Kb revealed its similarity to three human class I HLA molecules, consistent with the high primary sequence homology and common function of these peptide-presenting molecules. Electron density was located in the peptide-binding groove, to which a single peptide in a unique conformation was unambiguously fit. The peptide extends the length of the groove, parallel to the alpha-helices, and assumes an extended, mostly beta-strand conformation. The peptide is constrained within the groove by hydrogen bonding of its main-chain atoms and by contacts of its side chains with the H-2Kb molecule. The amino-terminal nitrogen atom of the peptide forms a hydrogen bond with the hydroxyl group of Tyr-171 of H-2Kb at one end of the groove, while the carboxyl-terminal oxygen forms a hydrogen bond with the hydroxyl group of Tyr-84 at the other end. Since the amino acids at both ends are conserved among human and mouse MHC molecules, this anchoring of each end of the peptide appears to be a general feature of peptide-MHC class I molecule binding and imposes restrictions on its length. The side chains of residues Tyr-3, Tyr-5, and Leu-8 of the VSV octapeptide fit into the interior of the H-2Kb molecule with no appreciable surface exposure, a finding in support of previous biological studies that showed the importance of these residues for binding. Thus, the basis for binding of specific peptide sequences to the MHC class I molecule is the steric restriction imposed on the peptide side chains by the architecture of the floor and sides of the groove. The side chains of Arg-1, Val-4, and Gln-6 and the main-chain of Gly-7 of the octapeptide are exposed on the surface of the complex, thus confirming their availability for T-cell receptor contact, as previously demonstrated by T-cell recognition experiments.
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PMID:Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition. 132 57

Feline leukemia viruses (FeLVs) belonging to the C subgroup induce aplastic anemia in domestic cats and have the ability, unique among FeLV strains, to proliferate in guinea pig fibroblasts in tissue culture. Previous studies have shown that the pathogenic and host range specificity of a prototype molecular clone of FeLV-C [FeLV-Sarma-C (FSC)] colocalize to a region encoding the 3' 73 amino acids of the pol gene product and the N-terminal 241 amino acids of the envelope surface glycoprotein named SU. Here, we amplified, via PCR, cloned, and sequenced the SU coding sequence from three additional anemia-inducing subgroup C FeLV isolates. Chimeric viruses were constructed by replacement of fragments of FeLV-C envelope genes into the FeLV-A prototype virus 61E. Using a modified vesicular stomatitis virus-FeLV pseudotype assay, we demonstrated that the subgroup C receptor specificity for each virus was determined by changes within the N-terminal 87-92 amino acids of SU, in which most changes occurred within the 15- to 20-amino-acid first variable region (V1). Determinants for growth in guinea pig cells colocalized to this region. Despite the consistent localization of biological determinants, the only consistent features that distinguished the deduced FeLV-A and FeLV-C proteins was one lysine-to-arginine change and a structural prediction of an alpha-helix in FeLV-A proteins versus random coil in FeLV-C proteins within V1. However, arginine in equilibrium with lysine substitutions were not sufficient to convert the subgroup A virus to the subgroup C phenotype or vice versa. Thus, certain distinct structural changes within the N-terminal region of FeLV SU can result in convergent viral phenotypes.
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PMID:Feline leukemia virus subgroup C phenotype evolves through distinct alterations near the N terminus of the envelope surface glycoprotein. 132 57

2'-5'-oligoadenylate synthetases constitute a multimember family of interferon-inducible enzymes which need double-stranded RNA as an obligatory cofactor. We have isolated cDNA clones for two new murine synthetases. These two clones, 9-2 and 3-9, encoded proteins of 414 and 363 amino acid residues, respectively, out of which the amino terminal 346 residues were almost identical. They were also very similar to the corresponding regions of human synthetases E16 and E18. On the other hand, the carboxyl-terminal 68 residues of clone 9-2 had no homology with the carboxyl-terminal residues of E18. These murine clones had only 67% amino acid identity with the previously isolated murine synthetase clone L3. 9-2 and 3-9 proteins were expressed efficiently by in vitro transcription and translation of cDNA clones containing the synthetase coding regions preceded by the 5'-untranslated region of the vesicular stomatitis virus NS gene. These in vitro synthetized proteins bound to double-stranded RNA and catalyzed the synthesis of 2'-5' oligoadenylates. A nested set of deletion mutants of the 9-2 clone was produced by restriction digestion and polymerase chain reaction. Functional testing of the corresponding truncated proteins revealed that a region between amino acid residues 104 and 158 was necessary for binding to double-stranded RNA and a region between residues 320 and 344 was necessary for enzyme activity. Moreover substitution of the lysine residue at position 333 by arginine did not affect the enzyme activity.
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PMID:Cloning, sequencing, and expression of two murine 2'-5'-oligoadenylate synthetases. Structure-function relationships. 165 24

TsO82, a spontaneous temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV) isolated in chick embryo fibroblasts (CEFs), complements the five prototype ts mutants of the virus. The data presented here indicate that the defect in tsO82 is localized in the M gene. The mutation changed a methionine to an arginine at position 51 of the M protein. Only true revertants could be isolated, and their frequency was low, perhaps due to the type of substitution required to return to the wild-type phenotype. TsO82 does not exhibit hypertranscription, in contrast to the data reported for all of the other ts mutants affected in the M protein. Moreover, tsO82 is conditionally ts, since it grows normally in BHK-21 cells at all temperatures. It exhibits no c.p.e. at the non-permissive temperature in CEFs. Our data argue for multiple functions of the M protein of VSV, the domain affected by the tsO82 mutation possibly being implicated both in the shut-off of cellular RNA synthesis, and for the recognition of a cellular factor required for efficient viral RNA synthesis.
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PMID:Genetic evidence for multiple functions of the matrix protein of vesicular stomatitis virus. 215 8

A cDNA copy of the mRNA for the glycoprotein G of Chandipura virus, a rhabdovirus, has been cloned, sequenced, and expressed in mammalian cells. The deduced amino acid sequence of G shows that the encoded protein is a typical transmembrane glycoprotein of 524 amino acids containing a cleavable amino-terminal signal peptide, two potential N-linked glycosylation sites, a hydrophobic membrane anchor domain near the carboxy terminus, and a cytoplasmic domain at the carboxy terminus. Somewhat unusual is the appearance of two charged amino acid residues, aspartate and arginine, within the putative membrane anchor sequence. Expression of the G gene in COS cells resulted in production of a glycosylated protein of mol wt 71,000 which was recognized by anti-Chandipura antibodies. Like the viral G protein, the expressed G contained covalently linked palmitic acid. However, unlike its vesicular stomatitis virus (Indiana serotype) counterpart, the Chandipura G protein has no potential palmitate-accepting cysteine residue within its cytoplasmic domain. Thus, the covalent attachment of fatty acid to this molecule may occur at one or both of the cysteines within the membrane anchor domain. The G protein was intracellularly transported to the cell surface and could induce cell fusion at low pH, showing that the expressed G protein was biologically active.
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PMID:Structure and expression of the glycoprotein gene of Chandipura virus. 274 47

A peptide corresponding to the amino-terminal 25 amino acids of the mature vesicular stomatitis virus glycoprotein has recently been shown to be a pH-dependent hemolysin. In the present study, we analyzed smaller constituent peptides and found that the hemolytic domain resides within the six amino-terminal amino acids. Synthesis of variant peptides indicates that the amino-terminal lysine can be replaced by another positively charged amino acid (arginine) but that substitution with glutamic acid results in the total loss of the hemolytic function. Peptide-induced hemolysis was dependent upon buffer conditions and was inhibited when isotonicity was maintained with mannitol, sucrose, or raffinose. In sucrose, all hemolytic peptides were also observed to mediate hemagglutination. The large 25-amino acid peptide is also a pH-dependent cytotoxin for mammalian cells and appears to effect gross changes in cell permeability. Conservation of the amino terminus of vesicular stomatitis virus and rabies virus suggests that the membrane-destabilizing properties of this domain may be important for glycoprotein function.
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PMID:Biologically active peptides of the vesicular stomatitis virus glycoprotein. 298 56

The membrane-spanning domain of the vesicular stomatitis virus glycoprotein (G protein) consists of a continuous stretch of 20 uncharged and mostly hydrophobic amino acids. We examined the effects of two mutations which change the amino acid sequence in this domain. These mutations were generated by oligonucleotide-directed mutagenesis of a cDNA clone encoding the G protein, and the altered G proteins were then expressed in animal cells. Replacement of an isoleucine residue in the center of this domain with a strongly polar but uncharged amino acid (glutamine) had no effect on membrane anchoring or transport of the protein to the cell surface. Replacement of this same isoleucine residue with a charged amino acid (arginine) generated a G protein that still spanned intracellular membranes but was not transported efficiently to the cell surface. The protein accumulated in the Golgi region in about 50% of the cells, and about 20% of the cells had detectable protein levels in a punctate pattern on the cell surface. In the remaining cells the protein accumulated in a vesicular pattern throughout the cytoplasm. Models which might explain the abnormal behavior of this protein are discussed.
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PMID:Incorporation of a charged amino acid into the membrane-spanning domain blocks cell surface transport but not membrane anchoring of a viral glycoprotein. 299 64


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