Abstract
Neuronal loss is frequently found in brains of
patients with human immunodeficiency virus
(HIV)-encephalopathy. Extensive apoptosis of
neurons is probably involved in the development of
HIV-encephalopathy. The present study was
designed to investigate the mechanism of neuronal
apoptosis. For this purpose, we examined autopsy
brains of two patients with HIV-encephalopathy.
Terminal deoxynucleotidyl transferase-mediated
dUTP nick-end labeling (TUNEL)-positive cells
and active forms of caspase-3- and -8-positive
cells, including neurons, were found in the
perivascular regions of the brains. In these
regions, TNF-related apoptosis-inducing ligand
(TRAIL)+ macrophages were also observed. We
also examined brains of HIV-1-infected mouse
model inoculated with human cells. In these
brains, TUNEL+ neurons were also found in the
perivascular region, the site where infiltrated HIV-1-
infected and TRAIL-expressing macrophages
were observed. Using an in vitro-culture system,
we also demonstrated that the HIV-1-infected
monocyte-derived macrophages preferentially
expressed TRAIL and that the addition of HIV-1-
infected macrophages or human TRAIL-overexpressing
mouse cells to cultured mouse primary
neurons/glia resulted in neuronal apoptosis. Our
results suggest the involvement of TRAIL
expressed on HIV-1-infected macrophages in the
induction of neuronal apoptosis in infected brain.
