Document 0748
 DOCN  M9460748
 TI    Central nervous system damage produced by expression of the HIV-1 coat
       protein gp120 in transgenic mice [see comments]
 DT    9404
 AU    Toggas SM; Masliah E; Rockenstein EM; Rall GF; Abraham CR; Mucke L;
       Department of Neuropharmacology, Scripps Research Institute, La; Jolla,
       California 92037.
 SO    Nature. 1994 Jan 13;367(6459):188-93. Unique Identifier : AIDSLINE
       MED/94159078
 CM    Comment in: Nature 1994 Jan 13;367(6459):113-4
 AB    Many people infected with human immunodeficiency virus type 1 (HIV-1)
       develop neurological complications that can culminate in dementia and
       paralysis. The discrepancy between the severity of impairment and the
       paucity of detectable HIV-1 within neurons has led to an intense search
       for diffusible virus- and host-derived factors that might be neurotoxic
       (see ref. 2 for review). The HIV-1 envelope glycoprotein gp120 is an
       extracellular protein that is shed from infected cells and so has the
       potential to diffuse and interact with distant uninfected brain cells.
       Studies on cultured immature cells suggest that gp120 induces
       neurotoxicity (reviewed in refs 2, 4), and systemic injection of gp120
       in neonatal rats and intracerebroventricular injection in adult rats
       results in deleterious effects on the brain. To assess the pathogenic
       potential of gp120 in the intact brain, we have now produced gp120 in
       the brains of transgenic mice and found a spectrum of neuronal and glial
       changes resembling abnormalities in brains of HIV-1-infected humans. 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.
 DE    Animal  Astrocytes/METABOLISM/PATHOLOGY  AIDS Dementia
       Complex/MICROBIOLOGY  Base Sequence
       Brain/METABOLISM/*MICROBIOLOGY/PATHOLOGY  Glial Fibrillary Acidic
       Protein/BIOSYNTHESIS  Human  HIV Envelope Protein
       gp120/BIOSYNTHESIS/*PHYSIOLOGY  HIV-1/*PATHOGENICITY  Mice  Mice,
       Transgenic  Microglia/PATHOLOGY  Molecular Sequence Data
       Neurons/PATHOLOGY  Recombinant Fusion Proteins/BIOSYNTHESIS  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).