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)

Zalcitabine is an analogue of the nucleoside deoxycytidine which, when intracellularly converted to an active triphosphate metabolite, inhibits replication of human immunodeficiency virus (HIV). Zalcitabine is thought to act in the early phase of HIV replication by inhibiting reverse transcriptase and terminating the viral DNA chain. In vitro, zalcitabine is one of the more effective nucleoside analogues currently in clinical use for HIV infection, with 0.5 mumol/L concentrations completely inhibiting HIV replication in human T lymphocyte cell lines. In clinical trials, p24 antigen levels decreased and CD4 cell counts increased in patients with acquired immunodeficiency syndrome (AIDS) receiving zalcitabine > or = 0.03 mg/kg/day as monotherapy. Dose-dependent adverse effects that include peripheral neuropathy, stomatitis and rash, restrict long term use at higher dosages, and it is unclear whether zalcitabine monotherapy is as effective as zidovudine in extending survival in HIV-infected patients. Alternating or concomitant therapy with zalcitabine and zidovudine provides effective inhibition of viral replication and disease progression (as measured by improvements in CD4 cell counts) with lower and less toxic dosage regimens. At present, therefore, zalcitabine has a place in AIDS therapy both in combination with zidovudine, and as monotherapy for patients unable to tolerate zidovudine.
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PMID:Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS). 128 Oct 77

Superinfection of H9 cells persistently infected with human immunodeficiency virus (HIV) with thermolabile vesicular stomatitis virus (VSV) or herpes simplex virus (HSV) led to the synthesis of hybrid progeny. These phenotypic mixtures were able to infect HeLa or Chinese hamster ovary cell lines, leading to the production of HIV p24 antigen and infectious HIV. This production was abrogated by prior incubation of the phenotypic mixtures with antiserum against VSV or HSV, as well as by incubation of the mixtures at 39 degrees C for 10 h. These results demonstrate that during coinfection of cells with either a RNA or DNA virus, HIV forms hybrid virions composed of the genetic information of HIV and the envelope glycoproteins of the coinfecting viruses.
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PMID:Phenotypic mixing between human immunodeficiency virus and vesicular stomatitis virus or herpes simplex virus. 215 77

Cell lines originally derived from malignant tumours of the brain were infected by diverse human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) isolates. By surface immunofluorescence it was shown that susceptible cells did not bear the CD4 antigen. They were also non-permissive for the formation of plaques by vesicular stomatitis virus pseudotypes and did not form syncytia with HIV-producing cells. Virus production was of low titre, and reverse transcriptase and the p24 antigen were consistently undetectable in the culture supernatants. Output virus could be detected by cocultivation with a sensitive T cell line, C8166, by the culture of supernatant medium with T cells and by detection of proviral HIV DNA after amplification. A higher multiplicity of input virus was required to establish a brain cell infection than was required for T lymphocytes or monocytes. Some HIV-susceptible brain cells contained mRNA for CD4 but infection was not blocked by anti-CD4 antibodies. Apparently HIV infection of these cells does not involve CD4 as the cellular receptor.
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PMID:Infection of brain cells by diverse human immunodeficiency virus isolates: role of CD4 as receptor. 267 35

The CD4 protein is required for the entry of human immunodeficiency virus (HIV) into target cells. Upon expression of the viral genome, three HIV-1 gene products participate in the removal of the primary viral receptor from the cell surface. To investigate the role of surface-CD4 in HIV replication, we have created a set of Jurkat cell lines which constitutively express surface levels of CD4 comparable to those found in peripheral blood lymphocytes and monocytes. Expression of low levels of CD4 on the surface of producer cells exerted an inhibitory effect on the infectivity of HIV-1 particles, whereas no differences in the amount of cell-free p24 antigen were observed. Higher levels of cell surface CD4 exerted a stronger inhibitory effect on infectivity, and also affected the release of free virus in experiments where the viral genomes were delivered by electrotransfection. The CD4-mediated inhibition of HIV-1 infectivity was not observed in experiments where the vesicular stomatitis virus G protein was used to pseudotype viruses, suggesting that an interaction between CD4 and gp120 is required for interference. In contrast, inhibition of particle release by high levels of cell-surface CD4 was not overcome by pseudotyping HIV-1 with foreign envelope proteins. Protein analysis of viral particles released from HIV-infected Jurkat-T cells revealed a CD4-dependent reduction in the incorporation of gp120. These results demonstrate that physiological levels of cell-surface CD4 interfere with HIV-1 replication in T cells by a mechanism that inhibits envelope incorporation into viral membranes, and therefore provide an explanation for the need to down-modulate the viral receptor in infected cells. Our findings have important implications for the spread of HIV in vivo and suggest that the CD4 down-modulation function may be an alternative target for therapeutic intervention.
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PMID:Cell surface CD4 interferes with the infectivity of HIV-1 particles released from T cells. 1170 77

Integration of the human immunodeficiency virus type 1 (HIV-1) genome into the host chromosome is a vital step in the HIV life cycle. The highly conserved cytosine-adenine (CA) dinucleotide sequence immediately upstream of the cleavage site is crucial for integrase (IN) activity. As this viral enzyme has an important role early in the HIV-1 replication cycle, interference with the IN substrate has become an attractive strategy for therapeutic intervention. We demonstrated that a designed zinc finger protein (ZFP) fused to green fluorescent protein (GFP) targets the 2-long terminal repeat (2-LTR) circle junctions of HIV-1 DNA with nanomolar affinity. We report now that 2LTRZFP-GFP stably transduced into 293T cells interfered with the expression of vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral red fluorescent protein (RFP), as shown by the suppression of RFP expression. We also used a third-generation lentiviral vector and pCEP4 expression vector to deliver the 2LTRZFP-GFP transgene into human T-lymphocytic cells, and a stable cell line for long-term expression studies was selected for HIV-1 challenge. HIV-1 integration and replication were inhibited as measured by Alu-gag real-time PCR and p24 antigen assay. In addition, the molecular activity of 2LTRZFP-GFP was evaluated in peripheral blood mononuclear cells. The results were confirmed by Alu-gag real-time PCR for integration interference. We suggest that the expression of 2LTRZFP-GFP limited viral integration on intracellular immunization, and that it has potential for use in HIV gene therapy in the future.
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PMID:Zinc finger protein designed to target 2-long terminal repeat junctions interferes with human immunodeficiency virus integration. 2242 8