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)

RMA/S is a mutant cell line with decreased cell surface expression of major histocompatibility complex class I molecules that has been reported to be deficient in presenting endogenously synthesized influenza virus nucleoprotein (NP) to cytotoxic T lymphocytes (CTL). In the present study we show that RMA/S cells can present vesicular stomatitis virus nucleocapsid protein, and, under some conditions, NP, to Kb-and Db-restricted CTL, respectively. Antigen presentation results from processing of cytosolic pools of endogenously synthesized proteins, and not the binding to cell surface class I molecules of antigenic peptides present in the virus inoculum or released from infected cells. Antigen processing of RMA/S differs, however, from processing by wild-type cells in requiring greater amounts of antigen, longer times to assemble or transport class I-peptide complexes, and in being more sensitive to blocking by anti-CD8 antibody. Thus, the antigen processing deficit in RMA/S cells is of a partial rather than absolute nature.
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PMID:RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes. 130 52

The nucleotide sequences of the fusion (F) gene of 15 clinical strains of human parainfluenza virus 3 (HPIV3) isolated between 1959 and 1987 were compared with the F gene sequence of the prototype strain, Wash/47885/57. Nucleotide sequence diversity was greatest in the noncoding regions of the F gene; however, regions believed to function as transcriptional signals were completely conserved. Amino acid sequences were highly conserved and all but a few amino acid substitutions were conservative in nature. Sequence comparisons indicate heterogeneity in HPIV3 F genes; however, a significant proportion of nucleotide changes are maintained after they first appear and seem to be accumulating with time. Phylogenetic analysis suggests that there are 2 lineages of HPIV3 in North America. The two lineages can be distinguished by specific amino acid differences in the F protein, which correlate with differences in antigenic properties and neutralization patterns of HPIV3. The pattern of HPIV3 evolution, based on the analysis of F gene sequences, most closely resembles that of influenza virus B, vesicular stomatitis virus and Newcastle disease virus.
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PMID:Evolution of the fusion protein gene of human parainfluenza virus 3. 131 Nov 37

Some but not all known Mx proteins possess intrinsic antiviral activity. The mouse genome contains two related interferon-regulated genes, designated Mx1 and Mx2. Mx1 codes for a nuclear 72-kDa protein which selectively interferes with the multiplication of influenza viruses. The Mx2 gene is crippled by a mutation in commonly used laboratory mouse strains and, hence, the antiviral potential of the Mx2 protein was unknown. We have corrected the frameshift mutation in a cloned Mx2 cDNA by site-directed mutagenesis. Expression of the repaired Mx2 cDNA in Swiss mouse 3T3 cells gave rise to an 80-kDa cytoplasmic protein that cross-reacted with antibodies to other Mx proteins. In contrast to the cases of mouse Mx1 and human Mx proteins, permanent cell lines were extremely unstable with respect to Mx2 expression. Analysis at the single-cell level revealed that mouse Mx2 conferred to the transfected cells a high degree of resistance to vesicular stomatitis virus, but had no inhibitory effect on influenza virus. The antiviral potential of mouse Mx2 is thus similar to that of rat Mx2 protein.
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PMID:Mouse Mx2 protein inhibits vesicular stomatitis virus but not influenza virus. 131 77

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

The interferon-induced Mx1 protein of mice confers selective resistance to influenza virus. It inhibits viral mRNA synthesis in the nucleus of influenza virus-infected cells. The related human MxA protein is localized in the cytoplasm and can inhibit influenza virus and vesicular stomatitis virus but not other viruses. MxA blocks a poorly defined cytoplasmic multiplication step of influenza virus that follows primary transcription of the viral genome. We previously showed that nuclear variants of MxA that carry an artificial nuclear translocation signal were also active against influenza virus. However, these variants blocked primary transcription of influenza virus. In the present study, we addressed the question of whether cytoplasmic forms of Mx1 were capable of mimicking the antiviral action of MxA by determining the antiviral activities of mutant mouse Mx1 protein. Cytoplasmic Mx1(E614), which differs from wild-type Mx1 by a single amino acid substitution in its nuclear transport signal, failed to inhibit the multiplication of influenza virus and vesicular stomatitis virus. Relocation of Mx1(E614) to the nucleus with the help of the simian virus 40 large T nuclear translocation signal attached to its amino terminus restored the influenza virus-inhibiting activity. Other changes in the carboxy-terminal region of Mx1 also abolished transport to the nucleus and simultaneously abolished antiviral activity. One of these variants, Mx1/A, gained activity against influenza virus upon relocation to the nucleus. These results demonstrate that unlike human MxA, the mouse Mx1 protein can function only in the nucleus. This finding has important implications regarding the mechanistic details of Mx protein action.
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PMID:Nuclear localization of mouse Mx1 protein is necessary for inhibition of influenza virus. 132 Dec 88

The fusion of lipid enveloped viruses with cellular membranes is thought to be mediated by the insertion into the target membrane of the N-terminal polypeptides of viral spike glycoproteins. Since membrane destabilization is a necessary step in membrane fusion, we investigated whether synthetic peptides with amino acid sequences corresponding to the N-termini of influenza virus hemagglutinin (HA2), vesicular stomatitis virus G-protein and Sendai virus F-protein, induce the destabilization and fusion of phospholipid vesicles. Membrane destabilization by the peptides was monitored by the release of aqueous contents of large unilamellar phospholipid vesicles. Aggregation was detected by a resonance energy transfer assay. Membrane fusion was followed by means of assays for the intermixing of phospholipids and of aqueous contents. The 17-amino acid HA2 peptide (HA2.17) destabilized phosphatidylcholine (PC) vesicles even at neutral pH, but the rate and extent of destabilization increased at lower pH. This peptide did not mediate appreciable release of contents from phosphatidylserine (PS) vesicles. HA2.17 induced neither aggregation nor fusion of PC or PS vesicles. In contrast, the 7-amino acid N-terminal peptide of G-protein (G.7) destabilized PS-containing membranes and not pure PC vesicles. Although G.7 caused aggregation of and lipid mixing between PS vesicles, it did not mediate any detectable intermixing of aqueous contents. The presence of cholesterol in PC membranes did not affect the destabilization caused by the N-terminal peptide of Sendai virus F-protein (F1.7), suggesting that cholesterol is not necessary for the effective interaction of this peptide with membranes, contrary to earlier proposals. Our results support the hypothesis that the hydrophobic N-terminal region of certain viral envelope proteins insert into and destabilize target membranes.
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PMID:Membrane destabilization by N-terminal peptides of viral envelope proteins. 132 86

We investigated a 73-kDa polypeptide (p73), a minor component of the rabies virion (HEP-Flury and ERA strains), accounting for as much as 1% of total virion proteins. Two-dimensional gel electrophoresis and immunoblotting with the antiserum against the heat shock protein 70 (hsp70) demonstrated that p73 was identical to a constitutive type of cellular hsp70. The antiserum also detected p73/hsp70 in the purified virions of other negative-stranded RNA viruses, such as vesicular stomatitis virus (New Jersey serotype), Newcastle disease virus (Miyadera strain), and influenza A virus (PR8 strain), among which, however, the contents were variable.
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PMID:Identification of heat shock protein 70 in the rabies virion. 132 9

The distributions of isoforms of the Na,K-ATPase alpha subunit were determined in mature cultured hippocampal neurons and in a polarized epithelial cell line. We find that hippocampal neurons express the alpha 1 and alpha 3 isoforms in the membranes of both axons and dendrites. In contrast the alpha 1 and alpha 3 proteins are exclusively basolateral when expressed endogenously or by stable transfection in renal epithelial cells. These data suggest that epithelial cells and hippocampal neurons localize these proteins by different mechanisms. These observations contrast with those made for the vesicular stomatitis virus and the influenza glycoproteins, which are polarized in both epithelial and neuronal cells.
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PMID:Isoforms of the Na,K-ATPase are present in both axons and dendrites of hippocampal neurons in culture. 132 55

T lymphocytes recognize antigens as peptide fragments associated with molecules encoded by the major histocompatibility complex (MHC) and expressed on the surface of antigen-presenting cells. In the thymus, T cells bearing alpha beta receptors that react with the MHC molecules expressed by radioresistant stromal elements are positively selected for maturation. In (A x B-->A) bone marrow chimaeras, T cells restricted to the MHC-A haplotype are positively selected, whereas MHC-B-reactive thymocytes are not. We investigated whether the introduction of particular thymic stromal elements bearing MHC-B molecules could alter the fate of B-reactive T cells in these (A x B-->A) chimaeras. Thymic epithelial cell (TEC) lines expressing H-2b were introduced by intrathymic injection into (H-2b/s-->H2s) bone marrow chimaeras and we measured their ability to generate H-2b-restricted cytotoxic T-lymphocytes (CTLs). We report here that one TEC line, 427.1, was able positively to select CTLs specific for influenza and vesicular stomatitis virus antigens in association with class I H-2b molecules. In addition, line 427.1 can process cytoplasmic proteins for presentation to H-2Kb- and H-2Db-restricted CTLs. Thus, a TEC line capable of normal class I MHC antigen processing and presentation in vitro can induce positive selection after intrathymic injection.
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PMID:Positive selection of T-lymphocytes induced by intrathymic injection of a thymic epithelial cell line. 133 4

The retinal pigment epithelium (RPE) is able to perform a variety of functions because of its high degree of plasma membrane polarity. Some aspects of this polarity such as the localization of the majority of Na-K ATPase to the apical membrane distinguish the RPE from kidney cells and most other transporting epithelia. The polarized budding of enveloped viruses such as vesicular stomatitis and influenza from the basolateral and apical membrane, respectively, has been used to study mechanisms underlying the domain-specific sorting of membrane proteins in cultured epithelial cell lines. These processes also serve as a useful index of the degree of polarization in epithelial cell cultures. Viral budding from apical and basolateral RPE membranes was used in this study to determine whether the sorting of viral envelope membrane proteins by the RPE is reversed in polarity from that of kidney cells and, if so, whether this might predict a fundamental difference in membrane protein sorting for RPE. The results clearly indicate that the polarity of viral membrane sorting and subsequent viral budding is the same in RPE as in other polarized epithelial cell lines examined to date.
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PMID:Polarized budding of vesicular stomatitis and influenza virus from cultured human and bovine retinal pigment epithelium. 133 32


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