CENTRAL-NERVOUS-SYSTEM DAMAGE PRODUCED BY EXPRESSION OF THE HIV-1 COAT PROTEIN GP120 IN TRANSGENIC MICE

Citation
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
Citations number
31
Categorie Soggetti
Multidisciplinary Sciences
Journal title
NatureACNP
ISSN journal
00280836
Volume
367
Issue
6459
Year of publication
1994
Pages
188 - 193
Database
ISI
SICI code
0028-0836(1994)367:6459<188:CDPBEO>2.0.ZU;2-P
Abstract
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.