14-3-3 Protein in CSF: An Early Predictor of SIV CNS Disease

In neurons, 14-3-3 proteins regulate diverse processes, including signal transduction, neurotransmitter production, and apoptosis by binding to target proteins, but the role 14-3-3 proteins play in the pathogenesis of central nervous system (CNS) disease remains unclear. To examine the relationship...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2005-03, Vol.64 (3), p.202-208
Main Authors: Helke, Kristi L, Queen, Suzanne E, Tarwater, Patrick M, Turchan-Cholewo, Jadwiga, Nath, Avindra, Zink, M Christine, Irani, David N, Mankowski, Joseph L
Format: Article
Language:English
Subjects:
14-3-3 Proteins - cerebrospinal fluid
Animals
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Astrocytes - metabolism
Astrocytes - virology
Axons - pathology
Axons - virology
Basal Ganglia - metabolism
Basal Ganglia - virology
Biological and medical sciences
Blotting, Western - methods
Cells, Cultured
Central Nervous System Diseases - cerebrospinal fluid
Central Nervous System Diseases - etiology
Central Nervous System Diseases - virology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Fetus
Gene Products, tat - pharmacology
Glial Fibrillary Acidic Protein - metabolism
Human immunodeficiency virus
Humans
Immunohistochemistry - methods
Infection - cerebrospinal fluid
Infection - complications
Infection - virology
Macaca
Macaca nemestrina
Macrophages - metabolism
Macrophages - virology
Medical sciences
Microglia - metabolism
Microglia - virology
Neurology
Neurons - metabolism
Neurons - virology
Ophthalmology
Retinopathies
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Simian Acquired Immunodeficiency Syndrome - cerebrospinal fluid
Simian Acquired Immunodeficiency Syndrome - complications
Simian Acquired Immunodeficiency Syndrome - virology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - isolation & purification
Simian Immunodeficiency Virus - physiology
Time Factors
Viral Envelope Proteins - metabolism
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Summary:In neurons, 14-3-3 proteins regulate diverse processes, including signal transduction, neurotransmitter production, and apoptosis by binding to target proteins, but the role 14-3-3 proteins play in the pathogenesis of central nervous system (CNS) disease remains unclear. To examine the relationship between presence of 14-3-3 protein in cerebrospinal fluid (CSF) and encephalitis in the SIV/macaque model of HIV CNS disease, CSF levels of 14-3-3 protein were measured by quantitative immunoblotting throughout infection in 6 SIV-infected pigtailed macaques. Beginning during asymptomatic infection and continuing until death, CSF levels of 14-3-3 were elevated in 4 of 6 SIV-infected animals. Animals with 14-3-3 protein in CSF had the highest viral loads in the CSF after acute infection and the highest levels of both viral RNA and protein in brain (p < 0.001). In contrast, the presence of 14-3-3 protein in CSF was not associated with CNS microglial/macrophage activation measured by quantitative immunohistochemical staining for CD68 (p = 0.13). CSF levels of 14-3-3 protein may be a valuable marker of early neuronal damage, CNS viral replication, and CNS disease progression in HIV-infected individuals.
ISSN:0022-3069
1554-6578
DOI:10.1093/jnen/64.3.202