1. MS-8209, a new Amphotericin B derivative that inhibits HIV-1 replication in vitro and restores T-cell activation via the CD3/TcR in HIV-infected CD4+ cells
- Author
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Magdalena Jung, Daniel Cefai, Fabienne Hadida, Patrice Debré, Michel Seman, and Jean-Gilles Vernin
- Subjects
Antigens, Differentiation, T-Lymphocyte ,CD4-Positive T-Lymphocytes ,CD3 Complex ,T cell ,CD3 ,Immunology ,HIV Core Protein p24 ,Receptors, Antigen, T-Cell ,HIV Envelope Protein gp120 ,Lymphocyte Activation ,Virus Replication ,Antiviral Agents ,Peripheral blood mononuclear cell ,Jurkat cells ,Cell Line ,Amphotericin B ,Calcium flux ,medicine ,Humans ,Immunology and Allergy ,biology ,T-cell receptor ,RNA-Directed DNA Polymerase ,Envelope glycoprotein GP120 ,Virology ,Molecular biology ,HIV Reverse Transcriptase ,Kinetics ,Infectious Diseases ,medicine.anatomical_structure ,Microscopy, Fluorescence ,Cell culture ,Type C Phospholipases ,HIV-1 ,biology.protein - Abstract
A new Amphotericin B derivative, MS-8209, which retains high antifungal activity with greatly reduced toxicity and improved solubility, has been developed. We investigated the antiviral properties of MS-8209 in Jurkat and CEM T-cell lines and in peripheral blood mononuclear cells infected in vitro with HIV-1BRU. Our results demonstrate, by determination of reverse transcriptase activity and p24 antigen level titration in cell culture supernatants, that MS-8209 inhibits HIV-1 replication in all cell types at concentrations without cytotoxicity. MS-8209 also prevents membrane expression of the HIV-1 large envelope glycoprotein gp120 and the decrease in CD4 level at the surface of infected cells. HIV-1-infected Jurkat cells exhibit a severe signalling defect at CD3 stimulation. Treatment with MS-8209 restores normal responsiveness at CD3 as assessed by measurement of inositol triphosphate accumulation and calcium flux. Finally, our results indicate that MS-8209 inhibits HIV-1BRU replication without preventing virus binding and penetration into target cells.
- Published
- 1991