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Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands
- Source :
- Nature Medicine. Dec, 2000, Vol. 6 Issue 12, p1380, 8 p.
- Publication Year :
- 2000
-
Abstract
- Neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). However, the underlying mechanisms remain largely unknown. Here we report that binding of HIV-1 transactivator (Tat) protein to low-density lipoprotein receptor-related protein (LRP) promoted efficient uptake of Tat into neurons. LRP-mediated uptake of Tat was followed by translocation to the neuronal nucleus. Furthermore, the binding of Tat to LRP resulted in substantial inhibition of neuronal binding, uptake and degradation of physiological ligands for LRP, including [alpha][sub.2]-macroglobulin, apolipoprotein E4, amyloid precursor protein and amyloid [beta]-protein. In a model of macaques infected with a chimeric strain of simian-human immunodeficiency virus, increased staining of amyloid precursor protein was associated with Tat expression in the brains of simian-human immunodeficiency virus-infected macaques with encephalitis. These results indicate that HIV-1 Tat may mediate HIV-1-induced neuropathology through a pathway involving disruption of the metabolic balance of LRP ligands and direct activation of neuronal genes.<br />Author(s): Ying Liu [1, 2]; Melina Jones [3]; Cynthia M. Hingtgen [1, 4]; Guojun Bu [5]; Nick Laribee [1]; Rudolph E. Tanzi [6]; Robert D. Moir [6]; Avindra Nath [3]; [...]
- Subjects :
- Amyloid beta-protein -- Health aspects
Amyloid beta-protein -- Genetic aspects
Amyloid beta-protein -- Research
HIV infection -- Genetic aspects
HIV infection -- Care and treatment
HIV infection -- Research
Low density lipoprotein receptors -- Health aspects
Low density lipoprotein receptors -- Genetic aspects
Low density lipoprotein receptors -- Research
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 6
- Issue :
- 12
- Database :
- Gale General OneFile
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.194151763