Casp8p41 expression in primary T cells induces a proinflammatory response

Julie A. Taylor, Nathan W. Cummins, Gary D. Bren, Stacey A. Rizza, Christopher P. Kolbert, Marshall D. Behrens, Keith L. Knutson, Jane C. Kahl, Yan W. Asmann, Andrew D. Badley

Research output: Contribution to journalArticle

4 Scopus citations

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 languageEnglish (US)
Pages (from-to)1251-1258
Number of pages8
JournalAIDS
Volume24
Issue number9
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Apoptosis
  • Casp8p41
  • HIV
  • Inflammation
  • Protease
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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