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.
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.
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