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

Lymphocytic choriomeningitis virus (LCMV) may cause a severe immunosuppression in mice. Its pathogenesis is apparently dependent on LCMV-specific CD8 effector T cells that mediate the destruction of virus-infected cells which are normally essentially involved in immune responses. Evaluation of various LCMV isolates in this study established a general correlation between their tropism for lymphohemopoietic cells and immunosuppression. When immune responses were assessed as the capacity of mice to mount an anti-vaccinia virus cytotoxic T cell response or an IgG response to vesicular stomatitis virus (VSV), after a primary LCMV infection, LCMV-Armstrong, WE, Clone 13 and Docile were increasingly immunosuppressive in a dose-dependent fashion with respect to both extent and duration. Analysis of lymphocyte subpopulations showed variable effects of the various LCMV isolates that did not reveal patterns readily explaining immunosuppression. To evaluate whether LCMV infection affected T and/or B cell functions directly or whether antigen presentation was impaired, adoptive transfer experiments were performed. Untreated or irradiated but uninfected normal recipient mice receiving adoptively transferred T or B cells from LCMV-WE or Docile-infected immunosuppressed donor mice responded within 30%-100% of normal ranges in both assay systems. In contrast, when T or B cells from normal donors were transferred to irradiated or non-irradiated LCMV-immunosuppressed recipients, they failed to mount a significant cytotoxic T cell response against vaccinia virus or an IgG response to VSV. Thus, the T and B cells from LCMV-immunosuppressed mice were able to function within normal ranges; in contrast, histologically and functionally, antigen presentation was severely impaired in LCMV-immunosuppressed mice.
 ...
PMID:Immunosuppression by lymphocytic choriomeningitis virus infection: competent effector T and B cells but impaired antigen presentation. 162 25

BALB/c mice and congenic H-2Ld-deficient BALB/c-H-2dm2 (dm2) mice were experimentally infected intranasally with isolates of vesicular stomatitis virus (VSV). The survival of infected hosts, viral replication in lungs and brains, and histopathologic in the two mouse strains were compared. In both strains of mice, mortality occurred during the period 7 to 10 days postinfection. However, dm2 mice were relatively resistant to lethal infections. Viral replication occurred at low levels in the lungs of both strains and did not evoke significant pathologic changes. In contrast, viral replication in the brains was much greater; in the BALB/c strain, this was accompanied by more frequent and more severe pathologic changes. In general, mice surviving at day 10 had effectively cleared virus from central nervous system but not respiratory sites. Evidence is presented that viral replication occurs first in the nasal cavity and is transmitted both to the lungs and to the olfactory bulb where focal cytopathology occurs. Virus enters the ventricles, causing encephalitis; necrosis occurs around the ventricles and in the lumbosacral region of the spinal cord. Necrotic lesions were accompanied by mononuclear infiltration. Mice immunized with virus of the same serotype or with a vaccinia virus hybrid encoding the VSV glycoprotein were protected from lethal infection; in contrast, mice immunized with heterotypic virus were susceptible to challenge.
 ...
PMID:Murine infection by vesicular stomatitis virus: initial characterization of the H-2d system. 165 14

The requirements for viral and host protein synthesis in the generation of target antigens for cytotoxic T lymphocytes (CTL) was evaluated by using vesicular stomatitis virus (VSV) inactivated by UV irradiation (UV-VSV). EL4 target cells incubated with UV-VSV were recognized and lysed by anti-VSV CTL, indicating that de novo synthesis of viral proteins was not required for the generation of antigens recognized by antiviral CTL. Anti-VSV CTL from H-2b mice primarily recognize determinants derived from the VSV N protein bound to the class I major histocompatibility complex (MHC) antigen H-2Kb. Comparison of a cloned CTL line representing this specificity and a heterogeneous population of anti-VSV CTL showed that determinants other than that recognized by the cloned CTL were generated more efficiently from UV-VSV. By using vaccinia virus recombinants that express deletion fragments of the N protein, it was shown that these additional determinants were probably derived from VSV proteins other than the N protein. The protein synthesis inhibitor emetine was used to determine whether newly synthesized host proteins were required for antigen generation. The addition of emetine to target cells prior to or at the time of the addition of UV-VSV inhibited lysis by anti-VSV CTL. This inhibition could be due to depletion of newly synthesized MHC molecules from intracellular membranes. This hypothesis was supported by using brefeldin A to delay membrane protein transport in target cells during the time of incubation with emetine and UV-VSV, which resulted in partial reversal of the effect of emetine. These results suggest that newly synthesized class I MHC molecules are required for the generation of antigens recognized by anti-VSV CTL.
 ...
PMID:Role of de novo protein synthesis in target cells recognized by cytotoxic T lymphocytes specific for vesicular stomatitis virus. 165 79

The protein kinase C inhibitor H-7 (2-20 microM) inhibited dose-dependently the infectivity of the vesicular stomatitis virus on cultured human fibroblasts. Electron microscopy showed that H-7 inhibited the viral entry. H-7 also inhibited the infectivity of four other enveloped viruses, herpes simplex I, turkey herpes, vaccinia and Sindbis. Similar results were obtained using staurosporine (2.5 nM), tamoxifen (40 microM), phloretin (140 microM), or W-7 (40 microM). However, the infectivity of non-enveloped viruses (e.g. poliomyelitis I) was not inhibited by H-7. These results show that protein kinase C is critically involved in the infectivity of enveloped viruses, most probably at the level of viral entry (receptor-mediated endocytosis).
 ...
PMID:Effects of protein kinase C inhibitors on viral entry and infectivity. 165 99

Anthraquinones and anthraquinone derivatives were characterized for their antiviral and virucidal activities against viruses representing several taxonomic groups. One of these compounds, hypericin, had activity against vesicular stomatitis virus, herpes simplex virus types 1 and 2, parainfluenza virus, and vaccinia virus (from 0.5 to 3.8 log10 reductions in infectivity) at concentrations of less than 1 microgram/ml as determined by a direct pre-infection incubation assay. Human rhinovirus was not sensitive to hypericin at concentrations up to 10 micrograms/ml. Addition of small amounts of Tween-80 to solutions containing hypericin enhanced, by up to 2.6 log10, hypericin's virucidal activity. Anthraquinones and anthraquinone derivatives with the hydroxyl and alkyl substitution pattern of emodin (i.e. emodin, emodin anthrone, emodin bianthrone and hypericin) were active against the enveloped viruses tested. The following general pattern of activity was found: hypericin greater than emodin bianthrone greater than emodin anthrone greater than emodin. Chrysophanic acid, aloe-emodin, and sennosides A and B did not possess activity against any of the viruses tested.
 ...
PMID:In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. 166 61

Carbocyclic cytidine (C-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [pox (vaccinia)], (+)RNA viruses [toga (Sindbis, Semliki forest), corona], (-)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), rhabdo (vesicular stomatitis)] and (+/-)RNA viruses (reo). The target enzyme of C-Cyd is supposed to be CTP synthetase that converts UTP to CTP. In keeping with this assumption are the observations that (i) C-Cyd effects a dose-dependent inhibition of RNA synthesis in both virus-infected and uninfected cells, and (ii) exogenous addition of either Urd or Cyd reverses both the antiviral and cytocidal activity of C-Cyd, whereas addition of dThd or dCyd fails to do so. The selectivity of C-Cyd against Sindbis, vesicular stomatitis and reo virus is markedly increased when C-Cyd is combined with Cyd (10 micrograms/mL). This combination may therefore be worth pursuing as a chemotherapeutic modality for the treatment of virus infections.
 ...
PMID:Broad-spectrum antiviral activity of carbodine, the carbocyclic analogue of cytidine. 168 59

BALB/c-H-2dm2 mice (H-2KdI-AdI-EdDd), a congenic strain of BALB/c mice, have a deletion of the class I MHC Ag, H-2Ld. This gene encodes the exclusive class I MHC-restricting gene product for vesicular stomatitis virus-specific cytolytic T lymphocytes. When dm2 mice were immunized with infectious vesicular stomatitis virus, a specific CTL response was generated. These CTL lysed VSV-infected targets that expressed Iad gene products, but not VSV-infected Iad- targets. The CTL were used initially as long term cytolytic lines; 13 CTL clones were derived by limit dilution. All of the clones expressed the phenotype CD3+, CD4+, CD8-; some clones expressed TCR that are members of the V beta 8 family, others did not. The clones were restricted by class II MHC Ag, both I-Ad and I-Ed serving as restricting elements for individual clones of the panel. All of the clones derived from dm2 mice were specific for the immunizing serotype, Indiana, of VSV and did not lyse syngeneic cells infected with VSV of the New Jersey serotype. Studies using defective interfering virus particles, UV light-inactivated virus, and purified micelles of the viral glycoprotein indicated that infectious virus was not required for sensitization of target cells for immune recognition by the class II MHC-restricted CTL clones. Additional studies using recombinant vaccinia virus vectors to sensitize targets confirmed the specificity of the clones for the viral glycoprotein. These studies also demonstrated a cryptic population of class II-restricted CTL in BALB/c lines specific for VSV G. Naturally occurring variant viruses and mutant viruses, selected for escape from neutralization by mAb, were used in an effort to map the determinant(s) recognized; on the basis of patterns of target cell lysis, three groups of epitopes recognized by the clones were defined. Therefore, in the absence of the class I MHC Ag required for a CTL response to VSV, dm2 mice generated CTL with the CD4+ phenotype that recognized different epitopes on the viral glycoprotein, and lysed cells in a class II-MHC restricted, Ag-specific manner.
 ...
PMID:Cytolytic T lymphocytes from the BALB/c-H-2dm2 mouse recognize the vesicular stomatitis virus glycoprotein and are restricted by class II MHC antigens. 169 51

Cyclopentenylcytosine (Ce-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [herpes (cytomegalo), pox (vaccinia)], (+)RNA viruses [picorna (polio, Coxsackie, rhino), toga (Sindbis, Semliki forest), corona], (-)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), arena (Junin, Tacaribe), rhabdo (vesicular stomatitis)] and (+/-)RNA viruses (reo). Ce-Cyd is a more potent antiviral agent than its saturated counterpart, cyclopentylcytosine (carbodine, C-Cyd). Ce-Cyd also has potent cytocidal activity against a number of tumor cell lines. The putative target enzyme for both the antiviral and antitumor action of Ce-Cyd is assumed to be the CTP synthetase that converts UTP to CTP. In keeping with this hypothesis was the finding that the antiviral and cytocidal effects of Ce-Cyd are readily reversed by Cyd and, to a lesser extent, Urd, but not by other nucleosides such as dThd or dCyd. In contrast, pyrazofurin and 6-azauridine, two nucleoside analogues that are assumed to interfere with OMP decarboxylase, another enzyme involved in the biosynthesis of pyrimidine ribonucleotides, potentiate the cytocidal activity of Ce-Cyd. Ce-Cyd should be further pursued, as such and in combination with OMP decarboxylase inhibitors, for its therapeutic potential in the treatment of both viral and neoplastic diseases.
 ...
PMID:Broad-spectrum antiviral and cytocidal activity of cyclopentenylcytosine, a carbocyclic nucleoside targeted at CTP synthetase. 171 Jan 19

T cell-mediated protection against a recombinant vaccinia virus was evaluated in mice with respect to the relative contributions of CTL vs that of T cell-dependent IL and of CD4+ cells. H-2b mice primed with the wildtype of vesicular stomatitis virus serotype Indiana (VSV-IND wt) mount an in vitro measurable cytotoxic response against the nucleoprotein (NP) of VSV-IND and are protected against a challenge infection with a vaccinia-VSV recombinant virus expressing the NP of VSV-IND (vacc-IND-NP). Their protective mechanism was highly susceptible to in vivo depletion of CD8+ T cells, but resistant to CD4+ depletion or treatment with anti-IFN-gamma and anti-TNF-alpha. Surprisingly, also VSV-CTL nonresponder H-2k mice were protected against a challenging infection with vacc-IND-NP when primed with VSV-IND wt. In contrast to the CTL responder H-2b mice, this protection was highly susceptible to CD4+ T cell depletion and to anti-IFN-gamma or anti-TNF-alpha treatment, but resistant to CD8+ T cell depletion. Antibodies were not responsible because they failed to transfer protection; in contrast CD4+ T cells conferred significant protection. VSV-CTL responder H-2b and nonresponder H-2k mice were protected almost equally well against a challenge dose of 10(3) pfu vacc-IND-NP inoculated intracerebrally. However, after intracerebral challenge with 5 x 10(6) pfu vacc-IND-NP, the CTL nonresponder mice died, whereas the CTL responder mice eliminated the virus by day 5. These results collectively show that CD4+ T cell-dependent IL may mediate antiviral protection, but their efficiency is relatively weak compared with CD8-mediated protection correlating with cytotoxic activity in vitro.
 ...
PMID:Antiviral protection by CD8+ versus CD4+ T cells. CD8+ T cells correlating with cytotoxic activity in vitro are more efficient in antivaccinia virus protection than CD4-dependent IL. 171 Feb 46

Novel neplanocin A analogues modified at the 6'-position, i.e., 6'-deoxy analogues (2, 3, 6, 9, 20), 6'-O-methylneplanocin A (15), and 6'-C-methylneplanocin A's (22a and 22b) have been synthesized and evaluated for their antiviral activity in a wide variety of DNA and RNA virus systems. These compounds showed an activity spectrum that conforms to that of S-adenosylhomocysteine hydrolase inhibitors. They were particularly active against pox- (vaccinia), paramyxo-(parainfluenza, measles, respiratory syncytial), arena- (Junin, Tacaribe), rhabdo- (vesicular stomatitis), reo-, and cytomegalovirus. In order of (increasing) antiviral activity, the compounds ranked as follows: 3 less than 15 approximately 20 less than 6 less than 9 approximately 2 less than 22a. Of the two diastereomeric forms of 22, only 22a was active; 22a surpassed neplanocin A both in antiviral potency and selectivity. Compound 22a appears to be a promising candidate drug for the treatment of pox-, paramyxo-, arena-, rhabdo-, reo-, and cytomegalovirus infections.
 ...
PMID:New neplanocin analogues. 1. Synthesis of 6'-modified neplanocin A derivatives as broad-spectrum antiviral agents. 173 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>