TY - JOUR
T1 - 14-3-3 Protein in CSF
T2 - An early predictor of SIV CNS disease
AU - Helke, Kristi L.
AU - Queen, Suzanne E.
AU - Tarwater, Patrick M.
AU - Turchan-Cholewo, Jadwiga
AU - Nath, Avindra
AU - Zink, M. Christine
AU - Irani, David N.
AU - Mankowski, Joseph L.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
KW - 14-3-3 protein
KW - CSF
KW - HIV
KW - Marker
KW - Neurodegeneration
KW - SIV
UR - http://www.scopus.com/inward/record.url?scp=15244341011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15244341011&partnerID=8YFLogxK
U2 - 10.1093/jnen/64.3.202
DO - 10.1093/jnen/64.3.202
M3 - Article
C2 - 15804051
AN - SCOPUS:15244341011
SN - 0022-3069
VL - 64
SP - 202
EP - 208
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 3
ER -