Tags

Type your tag names separated by a space and hit enter

Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands.
Nat Med. 2000 Dec; 6(12):1380-7.NMed

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 alpha2-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.

Authors+Show Affiliations

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11100124

Citation

Liu, Y, et al. "Uptake of HIV-1 Tat Protein Mediated By Low-density Lipoprotein Receptor-related Protein Disrupts the Neuronal Metabolic Balance of the Receptor Ligands." Nature Medicine, vol. 6, no. 12, 2000, pp. 1380-7.
Liu Y, Jones M, Hingtgen CM, et al. Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med. 2000;6(12):1380-7.
Liu, Y., Jones, M., Hingtgen, C. M., Bu, G., Laribee, N., Tanzi, R. E., Moir, R. D., Nath, A., & He, J. J. (2000). Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nature Medicine, 6(12), 1380-7.
Liu Y, et al. Uptake of HIV-1 Tat Protein Mediated By Low-density Lipoprotein Receptor-related Protein Disrupts the Neuronal Metabolic Balance of the Receptor Ligands. Nat Med. 2000;6(12):1380-7. PubMed PMID: 11100124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. AU - Liu,Y, AU - Jones,M, AU - Hingtgen,C M, AU - Bu,G, AU - Laribee,N, AU - Tanzi,R E, AU - Moir,R D, AU - Nath,A, AU - He,J J, PY - 2000/12/2/pubmed PY - 2001/2/28/medline PY - 2000/12/2/entrez SP - 1380 EP - 7 JF - Nature medicine JO - Nat Med VL - 6 IS - 12 N2 - 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 alpha2-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. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/11100124/Uptake_of_HIV_1_tat_protein_mediated_by_low_density_lipoprotein_receptor_related_protein_disrupts_the_neuronal_metabolic_balance_of_the_receptor_ligands_ L2 - https://doi.org/10.1038/82199 DB - PRIME DP - Unbound Medicine ER -