Membrane Expression of HIV Envelope Glycoproteins Triggers Apoptosis in CD4 Cells
| Autor: | Sylviane Muller, Yves Rivière, Bernard Krust, Anne G. Laurent-Crawford, Claude Desgranges, Charles Dauguet, Marie Paule Kieny, Ara G. Hovanessian |
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| Rok vydání: | 1993 |
| Předmět: |
CD4-Positive T-Lymphocytes
Programmed cell death viruses T cell Molecular Sequence Data Immunology Apoptosis HIV Envelope Protein gp120 Biology Genes env Giant Cells Viral envelope Viral entry Virology medicine Humans Amino Acid Sequence Protein Precursors Cytopathic effect Inhibitor of apoptosis domain Syncytium Cell Membrane virus diseases HIV Envelope Protein gp41 Clone Cells Cell biology Infectious Diseases medicine.anatomical_structure CD4 Antigens HIV-1 Protein Processing Post-Translational |
| Zdroj: | AIDS Research and Human Retroviruses. 9:761-773 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.1993.9.761 |
| Popis: | The cytopathic effect of HIV-1 and HIV-2 in CD4+ lymphocytes has been shown to be associated with apoptosis or programmed cell death. Using different experimental conditions, we demonstrate here that apoptosis is triggered by cell membrane expression of the mature HIV envelope glycoproteins, gp120-gp41 complex, and their interaction with CD4 receptor molecules. Viral entry alone did not induce apoptosis but virus replication was required in order to produce the gp120-gp41 complex. Indeed, expression of the HIV env gene alone in the CD4+ T cell line (CEM) was sufficient for the induction of apoptosis. In general, syncytium formation and apoptosis induction were closely associated as both events require functional envelope glycoproteins and CD4 molecules. Nevertheless, apoptosis but not syncytium formation was suppressed by a monoclonal antibody against CD4 that does not affect gp120 binding. Furthermore, single-cell killing by apoptosis was observed in infected cell cultures treated with a monoclonal antibody against gp41, which completely abolishes the formation of syncytia. These results indicate that apoptosis is not the consequence of toxic effects induced by the formation of syncytia but is triggered by the HIV envelope glycoproteins. Therefore, cell death during HIV infection in CD4+ lymphocyte cultures is due to a specific event triggered by the gp120-gp41 heterodimer complex programming death in metabolically active cells. |
| Databáze: | OpenAIRE |
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