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 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.
Helke
Kristi L
KL
Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Queen
Suzanne E
SE
Tarwater
Patrick M
PM
Turchan-Cholewo
Jadwiga
J
Nath
Avindra
A
Zink
M Christine
MC
Irani
David N
DN
Mankowski
Joseph L
JL
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D001369:Axons / Q000473:pathology / Q000821:virology; D001479:Basal Ganglia / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000821:virology; D004195:Disease Models, Animal; D005333:Fetus; D015696:Gene Products, tat / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007239:Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000821:virology; D008254:Macaca nemestrina; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D017628:Microglia / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid* / Q000150:complications / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000502:physiology; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000378:metabolism; D000097382:CD68 Molecule
D048948:14-3-3 Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015696:Gene Products, tat; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C094173:nuclear polyhedrosis virus gp41