Induction of cell death in human immunodeficiency virus-infected macrophages and resting memory CD4 T cells by trail/Apo2L

J. J. Lum, A. A. Pilon, J. Sanchez-Dardon, B. N. Phenix, J. E. Kim, J. Mihowich, K. Jamison, N. Hawley-Foss, D. H. Lynch, A. D. Badley

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Because the persistence of human immunodeficiency virus (HIV) in cellular reservoirs presents an obstacle to viral eradication, we evaluated whether tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/ Apo2L) induces apoptosis in such reservoirs. Lymphocytes and monocyte-derived macrophages (MDM) from uninfected donors do not die following treatment with either leucine zipper human TRAIL (LZhuTRAIL) or agonistic anti-TRAIL receptor antibodies. By contrast, such treatment induces apoptosis of in vitro HIV-infected MDM as well as peripheral blood lymphocytes from HIV-infected patients, including CD4+ CD45RO+ HLA-DR- lymphocytes. In addition, LZhuTRAIL-treated cells produce less viral RNA and p24 antigen than untreated controls. Whereas untreated cultures produce large amounts of HIV RNA and p24 antigen, of seven treated CD4+ CD45RO+ HLA-DR- cell cultures, viral RNA production was undetectable in all, p24 antigen was undetectable in six, and proviral DNA was undetectable in four. These data demonstrate that TRAIL induces death of cells from HIV-infected patients, including cell types which harbor latent HIV reservoirs.

Original languageEnglish (US)
Pages (from-to)11128-11136
Number of pages9
JournalJournal of virology
Volume75
Issue number22
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Lum, J. J., Pilon, A. A., Sanchez-Dardon, J., Phenix, B. N., Kim, J. E., Mihowich, J., Jamison, K., Hawley-Foss, N., Lynch, D. H., & Badley, A. D. (2001). Induction of cell death in human immunodeficiency virus-infected macrophages and resting memory CD4 T cells by trail/Apo2L. Journal of virology, 75(22), 11128-11136. https://doi.org/10.1128/JVI.75.22.11128-11136.2001