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Journal of Virology, November 2001, p. 11128-11136, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11128-11136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Cell Death in Human Immunodeficiency Virus-Infected Macrophages and Resting Memory CD4 T Cells by TRAIL/Apo2L

Julian J. Lum,1 André A. Pilon,1 Jaime Sanchez-Dardon,1 Barbara N. Phenix,1 John E. Kim,2 Jennifer Mihowich,2 Keri Jamison,2 Nanci Hawley-Foss,3 David H. Lynch,4 and Andrew D. Badley1,3,*

Ottawa Hospital Research Institute, University of Ottawa,1 National HIV/AIDS Laboratories, Health Canada,2 and Division of Infectious Diseases, Ottawa Hospital---General Campus,3 Ottawa, Ontario, Canada, and Immunex Corporation, Seattle, Washington4

Received 25 June 2001/Accepted 8 August 2001

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Ottawa Hospital Research Institute, 501 Smyth Rd., Ottawa, Ontario K1H 8L6, Canada. Phone: (613) 737-8998. Fax: (613) 737-8682. E-mail: abadley{at}ohri.ca.

Journal of Virology, November 2001, p. 11128-11136, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11128-11136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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