Article

14-3-3 protein in CSF: an early predictor of SIV CNS disease.

Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Journal of Neuropathology and Experimental Neurology (impact factor: 4.26). 03/2005; 64(3):202-8. pp.202-8
Source: PubMed

ABSTRACT 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.

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Keywords

6 SIV-infected animals
 
6 SIV-infected pigtailed macaques
 
central nervous system
 
cerebrospinal fluid
 
CNS disease progression
 
CNS microglial/macrophage activation
 
CNS viral replication
 
CSF levels
 
diverse processes
 
highest levels
 
highest viral loads
 
HIV CNS disease
 
neurotransmitter production
 
quantitative immunoblotting
 
quantitative immunohistochemical staining
 
role 14-3-3 proteins
 
signal transduction
 
SIV/macaque model
 
target proteins
 
valuable marker