Abstract
OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFκB). We have previously shown that Casp8p41-induced NFκB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41-induced NFκB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-γ were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV-infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection.
Original language | English (US) |
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Pages (from-to) | 1251-1258 |
Number of pages | 8 |
Journal | AIDS |
Volume | 24 |
Issue number | 9 |
DOIs | |
State | Published - Jun 1 2010 |
Keywords
- Apoptosis
- Casp8p41
- HIV
- Inflammation
- Protease
- Tumor necrosis factor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases