Flying in the Face of Resistance: Antiviral-independent Benefit of HIV Protease Inhibitors on T-cell Survival
| Autor: | David J. Schnepple, Alicia Algeciras-Schimnich, Gary D. Bren, Andrew D. Badley, Stacey R. Vlahakis, Sergey Trushin |
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| Rok vydání: | 2007 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptors CXCR4 Fas Ligand Protein Cell Survival viruses T cell HIV Envelope Protein gp120 Biology Virus Replication CXCR4 Fas ligand TNF-Related Apoptosis-Inducing Ligand Drug Resistance Viral medicine Humans HIV Protease Inhibitor Pharmacology (medical) Protease inhibitor (pharmacology) Cells Cultured Pharmacology chemistry.chemical_classification Nelfinavir Gene Products vpr virus diseases HIV Protease Inhibitors vpr Gene Products Human Immunodeficiency Virus biochemical phenomena metabolism and nutrition Flow Cytometry Virology Chemotaxis Leukocyte medicine.anatomical_structure chemistry Apoptosis Gene Products tat HIV-1 tat Gene Products Human Immunodeficiency Virus Tumor necrosis factor alpha Glycoprotein |
| Zdroj: | Clinical Pharmacology & Therapeutics. 82:294-299 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/sj.clpt.6100140 |
| Popis: | Human immunodeficiency virus (HIV) infection results in excessive apoptosis of infected and uninfected cells, mediated by host and viral factors present in plasma. As HIV protease inhibitors (PIs) have intrinsic antiapoptotic properties, we questioned whether HIV PIs could block HIV-induced CD4+ T-cell death independent of their effects on HIV replication. We demonstrate that HIV PIs block the death of CD4+ T cells induced by HIV glycoprotein 120 (gp120), Vpr, and Tat, as well as host signals Fas ligand, tumor necrosis factor, and tumor necrosis factor-related apoptosis-inducing ligand. Using gp120/CXCR4 as a model, we show that the HIV PIs specifically block mitochondrial apoptosis signaling. Furthermore, HIV PIs inhibit CD4+ T-cell death induced by viruses with high-level resistance to PIs (P |
| Databáze: | OpenAIRE |
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