Inhibition of HIV Infection by the Cytokine Midkine
| Autor: | Bernard Krust, Jean-Paul Briand, Ara G. Hovanessian, Sébastien Nisole, Christian Callebaut |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD3 Complex
T-Lymphocytes medicine.medical_treatment CD3 Cell Interferon-gamma Paracrine signalling CD28 Antigens Virology medicine Humans RNA Messenger Phytohemagglutinins Autocrine signalling Cells Cultured Midkine Dose-Response Relationship Drug biology Macrophages Proteins RNA-Binding Proteins CD28 Phosphoproteins Molecular biology Recombinant Proteins Cytokine medicine.anatomical_structure HIV-1 Leukocytes Mononuclear biology.protein Cytokines Interleukin-2 Carrier Proteins Peptides Nucleolin HeLa Cells |
| Zdroj: | Virology. 281(2):248-264 |
| ISSN: | 0042-6822 |
| DOI: | 10.1006/viro.2000.0767 |
| Popis: | The growth factor midkine (MK) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles. Here we show that synthetic and recombinant preparations of MK inhibit in a dose-dependent manner infection of cells by T-lymphocyte- and macrophage-tropic HIV-1 isolates. The binding of labeled MK to cells is prevented by excess unlabeled MK or by the anti-HIV pseudopeptide HB-19 that blocks HIV entry by forming a stable complex with the cell-surface-expressed nucleolin. MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors, while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL-2 or IFN-gamma and activation of T-lymphocytes by PHA or antibodies specific to CD3/CD28. In MK-producing lymphocytes, MK is detectable at the cell surface where it colocalizes with the surface-expressed nucleolin. Finally, by using MK-producing CD4(+) and CD4(-) cell clones we show that HIV infection in cell cultures could be inhibited in both an autocrine and a paracrine manner. The potent and distinct anti-HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli suggests that MK is a cytokine that could be implicated in HIV-induced pathogenesis. |
| Databáze: | OpenAIRE |
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