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)

Normal mice infected with 10(5) infectious doses of lymphocytic choriomeningitis virus (LCMV, WE isolate) generated a reduced or no T cell-independent IgM and/or T cell-dependent IgG response to a subsequent vesicular stomatitis virus Indiana (VSV-IND) injection; this transient immune suppression lasted for weeks to months. Connatally infected LCMV-carrier mice or acutely infected T cell-deficient nude mice had normal anti-VSV IgM and IgG or IgM responses respectively. LCMV-infected nude mice transfused with helper cell-depleted LCMV-specific immune spleen cells were immunosuppressed. Normal mice infected with LCMV but treated with a rat anti-CD8 mAb (that had been shown previously to eliminate cytotoxic T cells in vivo) and then infected with VSV exhibited a normal anti-VSV IgM and IgG response. Since no IFN-alpha or -beta was detected on, or after, day 6 of LCMV infection, neither LCMV alone, nor IFN induced by it caused the observed immune suppression; the presented evidence suggests that LCMV-immune CD8+ T cells were responsible for it. It is conceivable that a similar pathogenesis where virus-specific cytotoxic T cells may destroy virus-infected cells essentially involved in an immune response (APC, T helper cells, etc.) may be involved in other virally triggered immune suppression or in AIDS.
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PMID:Virus-triggered immune suppression in mice caused by virus-specific cytotoxic T cells. 296 46

Virus particles, lacking the spike G-glycoproteins, are produced during infection of Vero cells with the vesicular stomatitis virus mutant ts045 at the restrictive temperature 39.5 degrees C. At this temperature the mutated G proteins are blocked in their intracellular transport in the endoplasmic reticulum. We have studied the role of the G proteins in the formation of these spikeless virus particles. The results showed that the spikeless particles contain a full complement of membrane anchors, derived from the carboxy-terminal end of the G protein. Our observations suggest that virus particles are formed at the restrictive temperature with G protein which is later cleaved to produce spikeless particles. We suggest that this is due to a leak of G protein to the cell surface at 39.5 degrees C where budding then takes place, presumably driven by a G protein C-terminal tail--nucleocapsid interaction.
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PMID:The budding mechanism of spikeless vesicular stomatitis virus particles. 301 69

A human solvent-detergent (SD)-treated factor IX concentrate has been produced from cryoprecipitate-poor plasma using DEAE-Sepharose CL-6B and heparin-Sepharose CL-6B chromatography. The DEAE eluate was incubated with an SD mixture [0.3% tri(n-butyl) phosphate-1% Tween 80, 6-h at 24 degrees C] which was found to inactivate, in less than 1 h, more than 3.8 log10 of vesicular stomatitis virus and more than 4.8 log10 of Sindbis virus; the SD was removed by a subsequent heparin adsorption step. The specific activity of the concentrate was 10.9 +/- 1.3 IU factor IX: c/mg protein (n = 15). The factor IX coagulant to antigen ratio was 0.7 +/- 0.1. The concentrate was essentially free of factors II, VII and X, and protein C. The usual major contaminants of prothrombin complex concentrate (PCC) were absent: the concentrate contained about 94% alpha-1 proteins, and only 4 major proteins were resolved by SDS-PAGE (respective apparent molecular weight: 130, 86, 76 and 69 kilodaltons), and by crossed immunoelectrophoresis against an anti-PCC serum. The nonactivated partial thromboplastin time was equivalent to that of PCC; the product was devoid of factor IXa, of other activated procoagulant factors and of coagulant-active phospholipids (removed with SD in the heparin breakthrough fraction). Animal studies using the Wessler test and acute-toxicity test in rabbits revealed no adverse side effects. SD treatment could thus be used to inactivate viruses in factor IX concentrate and improve the safety of replacement therapy in hemophilia B.
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PMID:Large-scale production and properties of a solvent-detergent-treated factor IX concentrate from human plasma. 326 37

The matrix (M) protein of vesicular stomatitis virus (VSV) plays a central role in virus assembly by binding the nucleocapsid core to the viral envelope during the budding process. A small percentage of M protein molecules are phosphorylated in vivo, but the role of phosphorylation in M protein function is unknown. Using limited proteolysis, we previously determined the sites of in vivo phosphorylation for VSV M protein to be Thr 31 (and possibly Ser 32) and a site N-terminal to position 19 (Ser 2, Ser 3, or Ser 17) (P. E. Kaptur et al., J. Virol. 66, 5384-5392, 1992). M protein mutants were constructed using site-directed mutagenesis by substituting Ala for Ser or Thr at these sites in the M gene of the San Juan strain of VSV. One mutant had substitutions at the major in vivo phosphorylation site(s) at positions 31 and 32 (M31.32) while two others had additional substitutions at positions 2 and 3 (M2.3.31.32) or at position 17 (M17.31.32). Mutant M proteins were expressed in BHK cells using the vaccinia/T7 system, radiolabeled with 32Pi, and then analyzed for 32P content by PAGE and autoradiography. The data show that the site of phosphorylation near the N-terminus is at Ser 2 or 3 and not Ser 17. Further, Ser 38 was not phosphorylated. Mutation of the major phosphorylation site enhanced phosphorylation at alternative sites in the M protein C-terminal to amino acid 43 and at Ser residues 2 and 3. Mutant M proteins were tested for their ability to complement growth of the temperature-sensitive M protein mutant virus tsO23 at the nonpermissive temperature. Mutant M2.3.31.32 was further tested for its ability to assemble into VSV-defective interfering (DI) particles, using a replication system in which the DI genome and all five VSV proteins were expressed from plasmid DNA. Assembly of tsO23 virions or DI particles in the presence of mutant M proteins was similar to that observed for wild-type M proteins. These data indicate that phosphorylation of M protein at the major in vivo sites is not essential for virus assembly.
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PMID:Assembly functions of vesicular stomatitis virus matrix protein are not disrupted by mutations at major sites of phosphorylation. 785 2

Methods for inactivating virus contaminants in serum, cryoprecipitate-poor plasma, and protein concentrates need to be identified. In this study, vesicular stomatitis virus (VSV)-spiked human serum and cryoprecipitate-poor plasma were treated with cross-linked povidone iodine (XLPVPI) at concentrations of 0, 4, 6, 8, and 10 mg/mL up to 120 min at 4 and 24 degrees C. The activities of virus and relevant proteins were examined. The results indicated that XLPVPI at concentrations that inactivate > 5 logs of VSV in serum decreased factor IX and protein C activities by < 10% in cryoprecipitate-poor plasma. At concentrations up to 10 mg of XLPVPI/mL, < 10% of protein C and factor IX activity was lost after incubation for 5 min at 24 degrees C. In addition, < 10% loss in protein C and factor IX activity was observed at 4 degrees C after treatment with < or = 6 mg of XLPVPI/mL for 20 min. Treatment of human serum with 6 mg of XLPVPI/mL at 4 degrees C and 8 mg of XLPVPI/mL at 24 degrees C for 5 min provided inactivation of > 5 logs of VSV.
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PMID:Viral inactivation of vesicular stomatitis virus in normal human serum by cross-linked polyvinylpyrrolidone. 838 59

Since extensive degradation may be required to present complex Ags, we addressed whether macrophages (M phi) might function as APC for anti-viral cell-mediated immune responses. To study this question, murine splenic M phi were depleted by i.p. administration of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposomes or clodronate-liposomes) before priming mice with vesicular stomatitis virus (VSV). Cl2MDP-liposome treatment resulted in the rapid (1-day) depletion of splenic M phi that was associated with a suppression of the ability of M phi-deficient mice to generate secondary anti-VSV CTL and Th cell proliferative responses in vitro. Control studies demonstrated that splenic dendritic cells were not adversely affected by treatment with Cl2MDP-liposomes. To assess the contribution of splenic M phi subpopulations to T cell priming against this virus, priming was delayed following treatment with Cl2MDP-liposomes until specific M phi subsets had repopulated the spleen. This analysis revealed that repopulation by red pulp M phi, but not with other splenic M phi subsets, was associated with the ability to mount normal secondary CTL and Th cell responses against VSV. Depletion of splenic, but not resident, peritoneal M phi by i.v. injection of Cl2MDP-liposomes did not rescue T cell priming in VSV-infected mice. Thus, only red pulp M phi, and not other splenic or peritoneal M phi populations, are necessary for T cell priming to VSV, a biochemically complex Ag.
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PMID:T cell priming against vesicular stomatitis virus analyzed in situ: red pulp macrophages, but neither marginal metallophilic nor marginal zone macrophages, are required for priming CD4+ and CD8+ T cells. 902 12

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.
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PMID:[A case of hepatic metastasis of rectal cancer with familial adenomatous polyposis treated by transarterial administration of low-dose leucovorin and 5-FU]. 949 38

To examine possible interference patterns between immunodominant CTL Ags, we analyzed the response to mixtures of five well-characterized H-2Kb-restricted epitopes, each of which had earlier been described as immunodominant within its antigenic system. Clear patterns of dominance were observed between peptides in the mixture, with the CTL response focusing on the Sendai virus nucleoprotein 324-332 and vesicular stomatitis virus nucleoprotein 52-59 epitopes. The dominance of these epitopes correlated with high CTL availability. Subdominance of the OVA(257-264) and the MCF1233 murine leukemia virus envelope 574-581 peptides could not be explained by inferior ability to bind and stabilize MHC class I molecules. Interestingly, immunodominance was broken if the peptide mixture was pulsed on bone marrow-derived dendritic cells, a mode of immunization allowing efficient recognition of a broader set of specificities. Our results show that immunodominance is neither an absolute feature of a given epitope nor does it apply only in relation to other epitopes within the same protein, micro-organism, or cell. Novel "superdominant" hierarchies emerge in the response against multiple "dominant" epitopes. A T cell competition model to explain the data in terms of a balance influenced by CTL frequencies and available APC capacity is discussed.
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PMID:Superdominance among immunodominant H-2Kb-restricted epitopes and reversal by dendritic cell-mediated antigen delivery. 953 Dec 71

4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells. Here we report the immunological characterization of mice lacking 4-1BBL and of mice lacking both 4-1BBL and CD28. 4-1BBL-/- mice mount neutralizing IgM and IgG responses to vesicular stomatitis virus that are indistinguishable from those of wild-type mice. 4-1BBL-/- mice show unimpaired CTL responses to lymphocytic choriomeningitis virus (LCMV) and exhibit normal skin allograft rejection but have a weaker CTL response to influenza virus than wild-type mice. 4-1BBL-/-CD28-/- mice retain the CTL response to LCMV, respond poorly to influenza virus, and exhibit a delay in skin allograft rejection. In agreement with these in vivo results, allogeneic CTL responses of CD28-/- but not CD28+/+ T cells to 4-1BBL-expressing APC are substantially inhibited by soluble 4-1BB receptor as is the in vitro secondary response of CD28+ T cells to influenza virus peptides. TCR-transgenic CD28-/- LCMV glycoprotein-specific T cells are insensitive to the presence of 4-1BBL when a wild-type peptide is used, but the response to a weak agonist peptide is greatly augmented by the presence of 4-1BBL. These results further substantiate the idea that different immune responses vary in their dependence on costimulation and suggest a role for 4-1BBL in augmenting suboptimal CTL responses in vivo.
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PMID:Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. 1052 84

Links have been observed between infections and the development of autoimmunity. Proposed explanations include activation of self-Ag-bearing APC. Using a model system in which transgenic OVA is expressed in enterocytes, we showed that CD8 T cell recognition of cross-presented Ag in gut-associated lymph nodes was tolerogenic. However, concomitant infection with vesicular stomatitis virus encoding OVA abrogated tolerance and induced disease. We now show that following transfer of naive OT-I T cells, the addition of wild-type vesicular stomatitis virus, oral cholera toxin, or CD40 triggering can induce intestinal disease in transgenic mice. Tissue damage accompanied dramatic increases in cytokine release by activated OT-I cells in the intestine. The data indicated that products of antigenically unrelated infections can combine with cross-presented self-Ags on APC to prime autoaggressiveness, independent of additional Ag release. These results help explain how diverse pathogens, lacking any homology to self-proteins, could be causative agents in induction of organ-specific autoimmunity.
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PMID:Cutting edge: inflammatory signals drive organ-specific autoimmunity to normally cross-tolerizing endogenous antigen. 1247 Oct 97


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