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)

In vivo preinfection of chicks with rabies virus (RV) or vesicular stomatitis virus (VSV) ts 1026 inhibits tumour formation after superinfection with Rous sarcoma virus (RSV). The degree of inhibition depends on the titre of the infecting viruses and the interval between rhabdovirus and RSV infection. In vitro, cells preinfected with VSV ts 1026 under non-permissive conditions and superinfected with RSV, are not transformed as judged by cell morphology, serum requirement for growth or the capacity to form colonies in soft agar, all these being the same as in uninfected cells. Doubly infected cells take up less deoxyglucose than cells infected with RSV only and more than cells infected with VSV only. RSV multiplication in inhibited in doubly infected cells: the supernatant fluid of these cells contains fewer focus-forming units and less reverse transcriptase activity than that of cells infected with RSV only. Doubly infected cells contain both VSV and RSV internal antigens 15 days after infection. The supernatant fluid of cells infected with VSV and maintained under non-permissive conditions inhibits transformation by RSV and multiplication of RSV, but not of VSV. Under non-permissive conditions, the rhabdoviruses undergo at least part of the infectious cycle, but no infectious virus is produced. RV antigen can be detected in the brain of parenterally infected chicks and VSV antigen in cells infected 15 days previously. We conclude that the inhibition of RSV multiplication and expression is probably due to one or more processes linked to the persistence of rhabdovirus components and that it cannot be attributed exclusively to interferon.
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PMID:Inhibition of Rous sarcoma virus-induced transformation by preinfection with rhabdoviruses. 630 Feb 84

The ability of oligonucleotides to interact selectively with their targets is an important consideration in the design of antisense oligonucleotides. This is especially important in the case of antisense oligomers, such as psoralen-derivatized oligomers, which can irreversibly bind to their targets. We have studied the interactions of a series of psoralen-derivatized antisense oligonucleoside methylphosphonates with the mRNAs of vesicular stomatitis virus (VSV), mRNAs that have a high degree of sequence homology. Cross-linking reactions were carried out under conditions of low ionic strength in order to reduce mRNA secondary structure. A 12-mer, whose sequence was complementary to VSV M-mRNA and partially complementary to sequences found in N, NS, and G mRNA cross-linked extensively to N-message. On the other hand, 16-mers whose sequences were uniquely complementary to binding sites on N- or M-mRNA specifically and efficiently cross-linked to their targeted mRNAs over the temperature range 0 degree to 37 degrees C. A reverse transcriptase-catalyzed primer extension assay was used to show that one of the N-specific oligomers cross-linked at the expected site on N-mRNA and to estimate the extent of cross-linking. The results demonstrate that psoralen-derivatized oligonucleoside methylphosphonates can cross-link in a sequence-specific manner if the sequences of these oligomers are chosen carefully so as to avoid extensive partial complementarity with other mRNA sequences.
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PMID:Interactions of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates with vesicular stomatitis virus messenger RNA. 773 37

Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.
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PMID:Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection. 917 31

The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been reported to play a crucial role in the targeting of the Gag polyprotein precursor to the plasma membrane and in the incorporation of viral envelope glycoproteins into budding virions. In this report, we present evidence that mutation of a highly conserved Leu at matrix amino acid 20 blocks or markedly delays virus replication in a range of cell types, including T-cell lines, primary human peripheral blood mononuclear cells, and monocyte-derived macrophages. These mutations do not impair virus assembly and release, RNA encapsidation, or envelope glycoprotein incorporation into virions but rather cause significant defects in an early step in the virus life cycle, as measured by single-cycle infectivity assays and the analysis of viral DNA synthesis early postinfection. This infectivity defect is independent of the type of envelope glycoprotein carried on mutant virions; similar results are obtained in pseudotyping experiments using wild-type or truncated HIV-1 envelope glycoproteins, the amphotropic murine leukemia virus envelope, or the vesicular stomatitis G protein. Intriguingly, matrix residue 20 mutations also increase the apparent binding of Gag to membrane, accelerate the kinetics of Gag processing, and induce defects in endogenous reverse transcriptase activity without affecting virion density or morphology. These results help elucidate the function of matrix in HIV-1 replication.
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PMID:Role of matrix in an early postentry step in the human immunodeficiency virus type 1 life cycle. 955 1

In the absence of envelope gene expression, retrovirus packaging cell lines expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large amounts of noninfectious virus-like particles that contain reverse transcriptase, processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that these particles can be made infectious in an in vitro, cell-free system by the addition of a surrogate envelope protein, the G spike glycoprotein of vesicular stomatitis virus (VSV-G). The appearance of infectivity is accompanied by physical association of the G protein with the immature, noninfectious virus particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of the virus to titers similar to those of conventional VSV-G pseudotyped viruses. Furthermore, similar treatment of an amphotropic murine leukemia virus significantly allows infection of BHK cells not otherwise susceptible to infection with native amphotropic virus. The partially cell-free virus maturation system reported here should be useful for studies aimed at the preparation of tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid-envelope interactions during budding and of virus assembly and virus-receptor interactions during virus uptake into infected cells. It may also represent a potentially useful step toward the eventual development of a completely cell-free retrovirus assembly system.
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PMID:In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein. 965 75

A retroviral etiology might explain why amyloid plaque and/or spongiosis are or are not associated with neuronal death in prion diseases. While retroviral genes themselves may be responsible for neuronal death, a retrovirus may also cause mutations in cellular genes. Hence, the prion gene may be altered by a retrovirus in the same way as a cellular proto-oncogene is altered to produce an oncogene, either by transduction or by integration of the provirus in its vicinity. In both cases, the resulting abnormal prion protein, acting as a catalyst, may induce the formation of amyloid plaques. In addition, a wild type retrovirus may recombine to the vesicular stomatitis virus (VSV) to give rise to a pseudotyped retrovirus able to induce spongiosis. It is reported here that in scrapie, a blood monocytoid cell proliferates in vitro. If confirmed in other species, this raises the question of the potential link between prion disease and leukemia. Indeed neurovirulent strains of murine leukemia virus, a slow acting retrovirus, are known to induce spongiform encephalopathies. A preliminary attempt to purify reverse transcriptase by chromatography, using the classical protocol, failed because of the presence of a prion-like protein secreted by the blood mononuclear cells which stuck to the phosphocellulose column. Therefore, if a retrovirus is present in prion diseases, it would be evidenced only in animals developing the disease in the absence of prion protein. From this point of view, mice obtained in 1997 by the group of D. Dormont in France, offer a unique opportunity to test the retroviral hypothesis.
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PMID:Possible retroviral origin of prion disease: could prion disease be reconsidered as a preleukemia syndrome? 1022 Nov 68

The Spumaviridae (foamy viruses) are increasingly being considered as potential vectors for gene therapy, yet little has been documented of their basic cell biology. This study demonstrates that human foamy virus (HFV) has a broad tropism and that the receptor for HFV is expressed not only on many mammalian, but on avian and reptilian cells. Receptor interference assays using an envelope-expressing cell line and a vesicular stomatitis virus/HFV pseudotype virus demonstrate that the cellular receptor is common to all primate members of the genus. The majority of foamy virus particles assemble and remain sequestered intracellularly. A rapid and quantitative method of assaying foamy virus infectivity by reverse transcriptase activity facilitates the use of classical protocols to increase infectious virus titres in vitro to > or = 10(6) TCID/ml.
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PMID:Properties of human foamy virus relevant to its development as a vector for gene therapy. 1046 97

Human immunodeficiency virus (HIV) and Kaposi's sarcoma-associated herpesvirus (KSHV) coinfect many individuals in North America and in parts of Africa. Infection with HIV is a leading risk factor for the development of Kaposi's sarcoma (KS). In this study, we tested the hypothesis that HIV infection of common or adjacent cells would stimulate replication and spread of KSHV. Infection of a primary effusion lymphoma cell line by vesicular stomatitis virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-phase KSHV replication. Induction of lytic KSHV replication by HIV required active replication of HIV. The addition of the nucleoside reverse transcriptase inhibitor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibited the associated induction of KSHV lytic replication. Lytic replication occurred in both HIV-infected and HIV-uninfected cells within the culture, and could be induced in uninfected cells via a soluble factor released from the HIV-infected cells. Transmission of infectious KSHV to an uninfected target cell was enhanced by HIV replication and was inhibited by antiretroviral drugs. These results may have implications for the pathogenesis and treatment of KS in individuals coinfected with KSHV and HIV.
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PMID:Human immunodeficiency virus replication in a primary effusion lymphoma cell line stimulates lytic-phase replication of Kaposi's sarcoma-associated herpesvirus. 1055 51

Murine leukemia virus (MuLV)-derived retroviral vectors have had limited application in vascular gene therapy because of low transduction efficiency of vascular tissues, both in vitro and in vivo. In this study, we compared the gene transfer efficiency of two retroviral vectors: amphotropic MuLV and a MuLV vector pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) envelope. Target vascular tissues included human endothelial cells (EC), smooth muscle cells (SMC) and saphenous veins (SV). Transduction efficiency of human EC and SMC was significantly higher for VSV-G pseudotyped MuLV vector (90%) than for Amphotropic MuLV (20%). Luminal surface en face analysis of transduced cultured SV showed a six- to 10-fold greater transduction efficiency with VSV-G pseudotyped MuLV. The tissue plasminogen activator (tPA) gene was transduced into EC using each vector. Four days following transduction, a 12-fold higher tPA antigen concentration and a 38-fold higher tPA enzymatic activity was measured from cells transduced with the VSV-G pseudotyped vectors as compared with the amphotropic MuLV. There was no detectable pseudotransduction (protein transfer) associated with the VSV-G MuLV vector. Both AZT inhibition of reverse transcriptase and cell division arrest by gamma irradiation inhibited transduction, indicating that viral transduction correlated with RNA reverse transcription and cell proliferation. MuLV pseudotyped with the VSV-G envelope glycoprotein is an effective retroviral vector for vascular gene therapy.
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PMID:High efficiency in vitro gene transfer into vascular tissues using a pseudotyped retroviral vector without pseudotransduction. 1060 83

Nonreplicating vectors are being considered in HIV-1 vaccine design. However, nonreplicating viruses are typically weak immunogens, leading to efforts to target the vaccine to mature dendritic cells (DCs). We have studied a single-cycle form of HIV-1, prepared by pseudotyping envelope-defective HIV-1 plasmids with the envelope from vesicular stomatitis virus (VSV) G protein (VSV-G), to which most humans lack preexisting immunity. The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4. A majority of the cells reverse transcribed the HIV-1 RNA, and a minority expressed gag protein. The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls. Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated. Macrophages were much less efficient in expanding HIV-1-responsive T cells, and bulk mononuclear cells responded weakly to VSV/HIV-1. CD4(+) T cells from at least half of the donors showed strong responses to VSV/HIV-1-infected DCs. Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added. Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.
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PMID:Dendritic cells, infected with vesicular stomatitis virus-pseudotyped HIV-1, present viral antigens to CD4+ and CD8+ T cells from HIV-1-infected individuals. 1108 7


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