Sm. Toggas et al., CENTRAL-NERVOUS-SYSTEM DAMAGE PRODUCED BY EXPRESSION OF THE HIV-1 COAT PROTEIN GP120 IN TRANSGENIC MICE, Nature, 367(6459), 1994, pp. 188-193
MANY people infected with human immunodeficiency virus type 1 (HIV-1)
develop neurological complications that can culminate in dementia and
paralysis1. The discrepancy between the severity of impairment and the
paucity of detectable HIV-1 within neurons has led to an intense sear
ch for diffusible virus- and host-derived factors that might be neurot
oxic (see ref. 2 for review). The HIV-1 envelope glycoprotein gp120 is
an extracellular protein that is shed from infected cells3 and so has
the potential to diffuse and interact with distant uninfected brain c
ells. Studies on cultured immature cells suggest that gp120 induces ne
urotoxicity (reviewed in refs 2, 4), and systemic injection of gp120 i
n neonatal rats5 and intracerebroventricular injection in adult rats r
esults in deleterious effects on the brain6,7. To assess the pathogeni
c potential of gp120 in the intact brain, we have now produced gp120 i
n the brains of transgenic mice and found a spectrum of neuronal and g
lial changes resembling abnormalities in brains of HIV-1-infected huma
ns. The severity of damage correlated positively with the brain level
of gp120 expression. These results provide in vivo evidence that gp120
plays a key part in HIV-1-associated nervous system impairment. This
model should facilitate the evaluation and development of therapeutic
strategies aimed at HIV-brain interactions.