Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine monoclonal antibodies (Mabs) to the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were tested for their ability to inhibit the replication and spread of the virus in permanent cell cultures (Molt4/8, K37, H9) and in the culture of II-2 stimulated T cells of healthy donors. After addition of ascitic fluid containing monoclonal anti-p24 antibodies or purified anti-p24 antibodies or the respective control to co-cultures of infected and non-infected cells, HIV-1 replication was evaluated by determining the percentage of infected cells and the activity of reverse transcriptase (RT) in cell-free supernatant. In addition, the supernatant's infectivity was determined. FACS analysis demonstrated p24 antigen in about 40% of unfixed HIV-1 infected cells at the cell membrane. Monoclonal anti-p24 antibodies of different epitope specificity added to the cells but not to the virus delayed the spread of HIV-1 infection in permanent cell culture. Furthermore, anti-p24 Mabs inhibited the release of RT-active virus particles by HIV-1 infected cell lines or II-2 stimulated T-lymphocytes, respectively, up to 60%. The mode of action of anti-p24 antibodies after HIV-1 infection is discussed on the basis of the data obtained.
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PMID:Inhibition of HIV-1 infection in vitro by murine monoclonal anti-p24 antibodies. 162 12

Plasma membrane fluidity of intact peripheral blood lymphocytes (PBL) of phenytoin-treated nonepileptic patients and phenytoin-treated CD4+ lymphoid cells H9 and K37 was determined by fluorescence anisotropy measurements. Anisotropy values of the membrane probe 6-(9-anthroyloxy) stearic acid were decreased in all cell types as compared with controls, indicating increased plasma membrane fluidity of phenytoin-treated cells. Specific binding of 125I-labeled vasoactive intestinal peptide (VIP) to its cellular receptor CD4 on PBL was decreased in PBL of phenytoin-treated patients as compared with untreated, healthy subjects. Adsorption of a different ligand to the CD4 receptor on PBL, the human immunodeficiency virus type 1 (HIV-1), was likewise abolished to PBL of phenytoin-treated patients and phenytoin-treated CD4+ H9 and K37 cells, as assessed by indirect immunofluorescence. Subsequent HIV-1 infection of phenytoin-treated H9 and K37 cells was reduced as measured by indirect immunofluorescence and p24 antigen production. These data indicate that CD4 receptor availability for VIP and HIV-1 was reduced in phenytoin-treated cells. Using the DNA-specific dye Hoechst 33258, we examined cell cycle phase distributions of HIV-1 adsorbing and nonadsorbing H9 cells, as separated by flow cytometry. The majority of HIV-1 adsorbing cells were found to be in the G2/M phase, while nonadsorbing cells were mainly in the G0/G1 phase, during which plasma membrane fluidity is supposed to be increased. This study indicates that plasma membrane fluidization by phenytoin may serve to disrupt CD4 receptor function and emphasizes the impact of plasma membrane properties on HIV-1 adsorption and infection.
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PMID:Decreased binding of HIV-1 and vasoactive intestinal peptide following plasma membrane fluidization of CD4+ cells by phenytoin. 197 37

Human immunodeficiency virus regulatory protein Rev (regulator of viral expression) is translated from a monocistronic transcript produced early in the viral replication cycle. Rev binds to the cis-acting, highly structured viral RNA sequence Rev response element (RRE) and the Rev-RRE complex primarily controls nucleocytoplasmic transport of viral RNAs. Inhibition of Rev-RRE interaction therefore is an attractive target to block viral transport. We have developed a stable cell line carrying a lentiviral vector harboring a rev gene and a co-linear Rev-dependent GFP/luciferase reporter gene cassette and thus constitutively expressing the reporter proteins. Dose-dependent luciferase activity inhibition in the indicator cell line by known small molecule inhibitors Proflavin and K37 established the specificity of the assay. This novel single step assay, that involves use of very small amount of reagents/cells and addition of test material as the only manipulation, can therefore be useful for screening therapeutically potential Rev-RRE interaction inhibitors.
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PMID:A reporter based single step assay for evaluation of inhibitors targeting HIV-1 Rev-RRE interaction. 2442 16