Abstract

HIV-1 uses mononuclear phagocytes (monocytes, tissue macrophages, and dendritic cells) as a vehicle for its own dissemination and as a reservoir for continuous viral replication. The mechanism by which the host immune system clears HIV-1-infected macrophages is not understood. TRAIL may play a role in this process. TRAIL is expressed on the cell membrane of peripheral immune cells and can be cleaved into a soluble, secreted form. The plasma level of TRAIL is increased in HIV-1-infected patients, particularly those with high viral loads. To study the effect of elevated TRAIL on mononuclear phagocytes, we used recombinant human (rh) TRAIL and human monocyte-derived macrophages (MDM) as an in vitro model. Our results demonstrated rhTRAIL-induced apoptosis in HIV-1-infected MDM and inhibited viral replication, while having a reduced effect on uninfected MDM. HIV-1 infection significantly decreased Akt-1 phosphorylation; rhTRAIL exposure further decreased Akt-1 phosphorylation. Infection with a dominant-negative Akt-1 adenovirus potentiated rhTRAIL-induced apoptosis, while constitutively active Akt-1 blocked rhTRAIL-induced apoptosis in HIV-1-infected MDM. From this data we conclude the death ligand TRAIL preferentially provokes apoptosis of HIV-1-infected MDM, and the mechanism is reliant upon the inhibition of Akt-1 phosphorylation. Understanding this mechanism may facilitate the elimination of HIV-1-infected macrophages and lead to new therapeutic avenues for treatment of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)2304-2313
Number of pages10
JournalJournal of Immunology
Volume177
Issue number4
DOIs
StatePublished - Aug 15 2006

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HIV-1
Macrophages
Phosphorylation
Apoptosis
Phagocytes
HIV Infections
Viral Load
Adenoviridae
Dendritic Cells
Monocytes
Immune System
Cell Membrane
Ligands
Therapeutics
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

TRAIL-mediated apoptosis in HIV-1-infected macrophages is dependent on the inhibition of Akt-1 phosphorylation. / Huang, Yunlong; Erdmann, Nathan; Peng, Hui; Herek, Shelley; Davis, John S; Luo, Xu; Ikezu, Tsuneya; Zheng, Jialin C.

In: Journal of Immunology, Vol. 177, No. 4, 15.08.2006, p. 2304-2313.

Research output: Contribution to journalArticle

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AU - Huang, Yunlong

AU - Erdmann, Nathan

AU - Peng, Hui

AU - Herek, Shelley

AU - Davis, John S

AU - Luo, Xu

AU - Ikezu, Tsuneya

AU - Zheng, Jialin C

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