Journal of NeuroVirology

, Volume 18, Issue 5, pp 341–353

14-3-3s are potential biomarkers for HIV-related neurodegeneration

  • Diana Morales
  • Efthimios C. M. Skoulakis
  • Summer F. Acevedo
Review

Abstract

Over the last decade, it has become evident that 14-3-3 proteins are essential for primary cell functions. These proteins are abundant throughout the body, including the central nervous system and interact with other proteins in both cell cycle and apoptotic pathways. Examination of cerebral spinal fluid in humans suggests that 14-3-3s including 14-3-3ε (YWHAE) are up-regulated in several neurological diseases, and loss or duplication of the YWHAE gene leads to Miller–Dieker syndrome. The goal of this review is to examine the utility of 14-3-3s as a marker of human immune deficiency virus (HIV)-dependent neurodegeneration and also as a tool to track disease progression. To that end, we describe mechanisms implicating 14-3-3s in neurological diseases and summarize evidence of its interactions with HIV accessory and co-receptor proteins.

Keywords

14-3-3 Hepatitis C virus Neurocognition HIV accessory proteins gp120 Vpr Vpu GPR15 Nef 

Abbreviations

ACD

AIDS dementia complex

AD

Alzheimer's disease

ADHD

Attention deficient hyperactivity disorder

AIDS

Acquired immunodeficiency virus

BAD

B-cell lymphoma 2 antagonist of cell death

Bax

Bcl-2-associated X

BBB

Blood–brain barrier

Bcl-XL

B-cell lymphoma-extra large

C. elegans

Caenorhabditis elegans

Cdc25

Cell division cycle phosphatase 25

CDKs

Cyclin-dependent protein kinases

CJD

Creutzfeldt–Jakob disease

CME

Cytomegalovirus encephalitis

CNS

Central nervous system

CRK

Viral oncogene causes increased tyrosine-phosphorylated proteins

CSF

Cerebral spinal fluid

CXCR4

CXC chemokine receptor 4

DCAF-1

DNA binding protein 1 and Cullin 4a-associated factor

FoxO

Forkhead transcription factor

Gp120

Glycoprotein 120

GPR15

G protein receptor 15

GPRs

G protein cell receptors

HAD

HIV-associated dementia

HADC

HIV-associated dementia complex

HAND

HIV-associated neurocognitive disorders

HBMECs

Human brain microvascular endothelial cells

HCV

Hepatitis C virus

HEK293

Human embryonic kidney

Hela

Human cervical carcinoma

HepG2

Human hepatoma

HIV

Human immune deficiency virus

HIVE

HIV encephalitis

HMC

Human mesangial growth cells

HUVEC

Human umbilical vein endothelial cells

IL

Interleukin

ILK

Isolated lissencephaly

K2P

Potassium channel

LB

Lewy bodies

LIS1

Encodes subunit of platelet-activating factor acetylhydrolase 1B (PAFAH1B1)

MDS

Miller–Dieker syndrome

MS

Multiple sclerosis

MYO1C

Myosin-1C

Nef

Negative factor

PKA

Protein kinase A

PKC

Protein kinase C

Raf

Proto-oncogene serine/threonine-protein kinase

RNAi

RNA interference

S. pombe

Schizosaccharomyces pombe

siRNA

Single stranded RNA\

SIV

Simian immunodeficiency virus

TAU

Tubulin-associated unit

TUSC5

Tumor suppressor candidate 5

Vpr

Viral protein R

Vpu

Viral protein U

Ywhae/

Ywhae/14-3-3ε-deficient mice

YWHEA

14-3-3ε (human gene)

References

  1. Aitken A (2006) 14-3-3 proteins: a historic overview. Semin Cancer Biol 16:162–172PubMedCrossRefGoogle Scholar
  2. Aitken A, Amess B, Howell S, Jones D, Martin H, Patel Y, Robinson K, Toker A (1992a) The role of specific isoforms of 14-3-3 protein in regulating protein kinase activity in the brain. Biochem Soc Trans 20:607–611PubMedGoogle Scholar
  3. Aitken A, Collinge DB, van Heusden BP, Isobe T, Roseboom PH, Rosenfeld G, Soll J (1992b) 14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins. Trends Biochem Sci 17:498–501PubMedCrossRefGoogle Scholar
  4. Aitken A, Jones D, Soneji Y, Howell S (1995) 14-3-3 proteins: biological function and domain structure. Biochem Soc Trans 23:605–611PubMedGoogle Scholar
  5. Aitken A, Baxter H, Dubois T, Clokie S, Mackie S, Mitchell K, Peden A, Zemlickova E (2002) Specificity of 14-3-3 isoform dimer interactions and phosphorylation. Biochem Soc Trans 30:351–360PubMedCrossRefGoogle Scholar
  6. Anand P, Springer SA, Copenhaver MM, Altice FL (2010) Neurocognitive impairment and HIV risk factors: a reciprocal relationship. AIDS Behav 14:1213–1226PubMedCrossRefGoogle Scholar
  7. Aoki H, Hayashi J, Moriyama M, Arakawa Y, Hino O (2000) Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1. J Virol 74:1736–1741PubMedCrossRefGoogle Scholar
  8. Bahl JM, Heegaard NH, Falkenhorst G, Laursen H, Hogenhaven H, Molbak K, Jespersgaard C, Hougs L, Waldemar G, Johannsen P, Christiansen M (2008) The diagnostic efficiency of biomarkers in sporadic Creutzfeldt–Jakob disease compared to Alzheimer's disease. Neurobiol Aging 30(11):1834–1841PubMedCrossRefGoogle Scholar
  9. Banerjee A, Meyer K, Mazumdar B, Ray RB, Ray R (2010) Hepatitis C virus differentially modulates activation of forkhead transcription factors and insulin-induced metabolic gene expression. J Virol 84:5936–5946PubMedCrossRefGoogle Scholar
  10. Bartosik-Psujek H, Archelos JJ (2004) Tau protein and 14-3-3 are elevated in the cerebrospinal fluid of patients with multiple sclerosis and correlate with intrathecal synthesis of IgG. J Neurol 251:414–420PubMedCrossRefGoogle Scholar
  11. Baxter HC, Fraser JR, Liu WG, Forster JL, Clokie S, Steinacker P, Otto M, Bahn E, Wiltfang J, Aitken A (2002a) Specific 14-3-3 isoform detection and immunolocalization in prion diseases. Biochem Soc Trans 30:387–391PubMedCrossRefGoogle Scholar
  12. Baxter HC, Liu WG, Forster JL, Aitken A, Fraser JR (2002b) Immunolocalisation of 14-3-3 isoforms in normal and scrapie-infected murine brain. Neuroscience 109:5–14PubMedCrossRefGoogle Scholar
  13. Bazan HA, Alkhatib G, Broder CC, Berger EA (1998) Patterns of CCR5, CXCR4, and CCR3 usage by envelope glycoproteins from human immunodeficiency virus type 1 primary isolates. J Virol 72:4485–4491PubMedGoogle Scholar
  14. Belzile JP, Duisit G, Rougeau N, Mercier J, Finzi A, Cohen EA (2007) HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4AVPRBP E3 ubiquitin ligase. PLoS Pathog 3:e85PubMedCrossRefGoogle Scholar
  15. Berg D, Holzmann C, Riess O (2003a) 14-3-3 proteins in the nervous system. Nat Rev Neurosci 4:752–762PubMedCrossRefGoogle Scholar
  16. Berg D, Riess O, Bornemann A (2003b) Specification of 14-3-3 proteins in Lewy bodies. Ann Neurol 54:135PubMedCrossRefGoogle Scholar
  17. Bernier V, Lagace M, Bichet DG, Bouvier M (2004) Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol Metab 15:222–228PubMedCrossRefGoogle Scholar
  18. Bertrand A, Brandel JP, Grignon Y, Sazdovitch V, Seilhean D, Faucheux B, Privat N, Brault JL, Vital A, Uro-Coste E, Pluot M, Chapon F, Maurage CA, Letournel F, Vespignani H, Place G, Degos CF, Peoc'h K, Haik S, Hauw JJ (2009) Wernicke encephalopathy and Creutzfeldt–Jakob disease. J Neurol 256:904–909PubMedCrossRefGoogle Scholar
  19. Bi W, Sapir T, Shchelochkov OA, Zhang F, Withers MA, Hunter JV, Levy T, Shinder V, Peiffer DA, Gunderson KL, Nezarati MM, Shotts VA, Amato SS, Savage SK, Harris DJ, Day-Salvatore DL, Horner M, Lu XY, Sahoo T, Yanagawa Y, Beaudet AL, Cheung SW, Martinez S, Lupski JR, Reiner O (2009) Increased LIS1 expression affects human and mouse brain development. Nat Genet 41:168–177PubMedCrossRefGoogle Scholar
  20. Bica I, McGovern B, Dhar R, Stone D, McGowan K, Scheib R, Snydman DR (2001) Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 32:492–497PubMedCrossRefGoogle Scholar
  21. Bolton DL, Barnitz RA, Sakai K, Lenardo MJ (2008) 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr. Biol Direct 3:17PubMedCrossRefGoogle Scholar
  22. Boston PF, Jackson P, Thompson RJ (1982) Human 14-3-3 protein: radioimmunoassay, tissue distribution, and cerebrospinal fluid levels in patients with neurological disorders. J Neurochem 38:1475–1482PubMedCrossRefGoogle Scholar
  23. Brandel JP, Delasnerie-Laupretre N, Laplanche JL, Hauw JJ, Alperovitch A (2000) Diagnosis of Creutzfeldt–Jakob disease: effect of clinical criteria on incidence estimates. Neurology 54:1095–1099PubMedCrossRefGoogle Scholar
  24. Bruno DL, Anderlid BM, Lindstrand A, van Ravenswaaij-Arts C, Ganesamoorthy D, Lundin J, Martin CL, Douglas J, Nowak C, Adam MP, Kooy RF, Van der Aa N, Reyniers E, Vandeweyer G, Stolte-Dijkstra I, Dijkhuizen T, Yeung A, Delatycki M, Borgstrom B, Thelin L, Cardoso C, van Bon B, Pfundt R, de Vries BB, Wallin A, Amor DJ, James PA, Slater HR, Schoumans J (2010) Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes. J Med Genet 47:299–311PubMedCrossRefGoogle Scholar
  25. Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J, Gross A, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB, Ledbetter DH (2003) Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller–Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3. Am J Hum Genet 72:918–930PubMedCrossRefGoogle Scholar
  26. Castellani RJ, Colucci M, Xie Z, Zou W, Li C, Parchi P, Capellari S, Pastore M, Rahbar MH, Chen SG, Gambetti P (2004) Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt–Jakob disease. Neurology 63:436–442PubMedCrossRefGoogle Scholar
  27. Chitravas N, Jung RS, Kofskey DM, Blevins JE, Gambetti P, Leigh RJ, Cohen ML (2011) Treatable neurological disorders misdiagnosed as Creutzfeldt–Jakob disease. Ann Neurol 70:437–444PubMedCrossRefGoogle Scholar
  28. Chohan G, Pennington C, Mackenzie JM, Andrews M, Everington D, Will RG, Knight RS, Green AJ (2010) The role of cerebrospinal fluid 14-3-3 and other proteins in the diagnosis of sporadic Creutzfeldt–Jakob disease in the UK: a 10-year review. J Neurol Neurosurg Psychiatry 81:1243–1248PubMedCrossRefGoogle Scholar
  29. Chung JJ, Okamoto Y, Coblitz B, Li M, Qiu Y, Shikano S (2009) PI3K/Akt signalling-mediated protein surface expression sensed by 14-3-3 interacting motif. FEBS J 276:5547–5558PubMedCrossRefGoogle Scholar
  30. Cohen EA, Terwilliger EF, Sodroski JG, Haseltine WA (1988) Identification of a protein encoded by the vpu gene of HIV-1. Nature 334:532–534PubMedCrossRefGoogle Scholar
  31. Cohen EA, Dehni G, Sodroski JG, Haseltine WA (1990a) Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol 64:3097–3099PubMedGoogle Scholar
  32. Cohen EA, Terwilliger EF, Jalinoos Y, Proulx J, Sodroski JG, Haseltine WA (1990b) Identification of HIV-1 vpr product and function. J Acquir Immune Defic Syndr 3:11–18PubMedGoogle Scholar
  33. Collins SJ, McGlade A, Boyd A, Masters CL, Klug GM (2010) 14-3-3 protein detection and sporadic CJD: the status quo serves well while awaiting progress. J Neurol Neurosurg Psychiatry 81:1181PubMedCrossRefGoogle Scholar
  34. Creutzfeld HG (1920) Uber eine egenartige herdformige erkrankung des zentralnervensystems. Neurol Psychiatr 57:1–18CrossRefGoogle Scholar
  35. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME (2000) 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 6:41–51PubMedGoogle Scholar
  36. de Seze J, Peoc'h K, Ferriby D, Stojkovic T, Laplanche JL, Vermersch P (2002) 14-3-3 Protein in the cerebrospinal fluid of patients with acute transverse myelitis and multiple sclerosis. J Neurol 249:626–627PubMedCrossRefGoogle Scholar
  37. Dube M, Bego MG, Paquay C, Cohen EA (2010) Modulation of HIV-1-host interaction: role of the Vpu accessory protein. Retrovirology 7:114PubMedCrossRefGoogle Scholar
  38. Dunham JH, Hall RA (2009) Enhancement of the surface expression of G protein-coupled receptors. Trends Biotechnol 27:541–545PubMedCrossRefGoogle Scholar
  39. Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y (2001) HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25. Virology 287:359–370PubMedCrossRefGoogle Scholar
  40. Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44PubMedCrossRefGoogle Scholar
  41. Everall IP, Luthert PJ, Lantos PL (1993) Neuronal number and volume alterations in the neocortex of HIV infected individuals. J Neurol Neurosurg Psychiatry 56:481–486PubMedCrossRefGoogle Scholar
  42. Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, Sun Y, Barrett P, Marchand N, Sullivan N, Gerard N, Gerard C, Sodroski J (1997) Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J Exp Med 186:405–411PubMedCrossRefGoogle Scholar
  43. Fiorini M, Zanusso G, Benedetti MD, Righetti PG, Monaco S (2007) Cerebrospinal fluid biomarkers in clinically isolated syndromes and multiple sclerosis. Proteomics Clin Appl 1:963–971PubMedCrossRefGoogle Scholar
  44. Fong WH, Tsai HD, Chen YC, Wu JS, Lin TN (2010) Anti-apoptotic actions of PPAR-gamma against ischemic stroke. Mol Neurobiol 41:180–186PubMedCrossRefGoogle Scholar
  45. Foster JL, Denial SJ, Temple BR, Garcia JV (2011) Mechanisms of HIV-1 Nef function and intracellular signaling. J Neuroimmune Pharmacol 6:230–246PubMedCrossRefGoogle Scholar
  46. Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647PubMedCrossRefGoogle Scholar
  47. Gallo SA, Finnegan CM, Viard M, Raviv Y, Dimitrov A, Rawat SS, Puri A, Durell S, Blumenthal R (2003) The HIV Env-mediated fusion reaction. Biochim Biophys Acta 1614:36–50PubMedCrossRefGoogle Scholar
  48. Gelman BB, Nguyen TP (2010) Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: proteomic analysis of human synaptosomes. J Neuroimmune Pharmacol 5:92–102PubMedCrossRefGoogle Scholar
  49. Goff SP (2007) Host factors exploited by retroviruses. Nat Rev Microbiol 5:253–263PubMedCrossRefGoogle Scholar
  50. Goh WC, Rogel ME, Kinsey CM, Michael SF, Fultz PN, Nowak MA, Hahn BH, Emerman M (1998) HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 4:65–71PubMedCrossRefGoogle Scholar
  51. Green AJ, Thompson EJ, Stewart GE, Zeidler M, McKenzie JM, MacLeod MA, Ironside JW, Will RG, Knight RS (2001) Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 70:744–748PubMedCrossRefGoogle Scholar
  52. Hashiguchi M, Sobue K, Paudel HK (2000) 14-3-3zeta is an effector of tau protein phosphorylation. J Biol Chem 275:25247–25254PubMedCrossRefGoogle Scholar
  53. He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR (1995) Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 69:6705–6711PubMedGoogle Scholar
  54. Helke KL, Queen SE, Tarwater PM, Turchan-Cholewo J, Nath A, Zink MC, Irani DN, Mankowski JL (2005) 14-3-3 protein in CSF: an early predictor of SIV CNS disease. J Neuropathol Exp Neurol 64:202–208PubMedGoogle Scholar
  55. Hernandez MD, Sherman KE (2011) HIV/hepatitis C coinfection natural history and disease progression. Curr Opin HIV AIDS 6:478–482PubMedCrossRefGoogle Scholar
  56. Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG (1996) The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 335:924–930PubMedCrossRefGoogle Scholar
  57. Hsu K, Seharaseyon J, Dong P, Bour S, Marban E (2004) Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel. Mol Cell 14:259–267PubMedCrossRefGoogle Scholar
  58. Huang N, Marie SK, Livramento JA, Chammas R, Nitrini R (2003) 14-3-3 protein in the CSF of patients with rapidly progressive dementia. Neurology 61:354–357PubMedCrossRefGoogle Scholar
  59. Hyon C, Marlin S, Chantot-Bastaraud S, Mabboux P, Beaujard MP, Al Ageeli E, Vazquez MP, Picard A, Siffroi JP, Portnoi MF (2011) A new 17p13.3 microduplication including the PAFAH1B1 and YWHAE genes resulting from an unbalanced X;17 translocation. Eur J Med Genet 54:287–291PubMedCrossRefGoogle Scholar
  60. Ikeda M, Hikita T, Taya S, Uraguchi-Asaki J, Toyo-oka K, Wynshaw-Boris A, Ujike H, Inada T, Takao K, Miyakawa T, Ozaki N, Kaibuchi K, Iwata N (2008) Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum Mol Genet 17:3212–3222PubMedCrossRefGoogle Scholar
  61. Irani DN, Kerr DA (2000) 14-3-3 protein in the cerebrospinal fluid of patients with acute transverse myelitis. Lancet 355:901PubMedCrossRefGoogle Scholar
  62. Iskander S, Walsh KA, Hammond RR (2004) Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia. J Neuroinflammation 1:7PubMedCrossRefGoogle Scholar
  63. Jones G, Power C (2006) Regulation of neural cell survival by HIV-1 infection. Neurobiol Dis 21:1–17PubMedCrossRefGoogle Scholar
  64. Jones GJ, Barsby NL, Cohen EA, Holden J, Harris K, Dickie P, Jhamandas J, Power C (2007) HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration. J Neurosci 27:3703–3711PubMedCrossRefGoogle Scholar
  65. Kapasi AA, Fan S, Singhal PC (2001) Role of 14-3-3epsilon, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation. Am J Physiol Renal Physiol 280:F333–F342PubMedGoogle Scholar
  66. Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC (1991) Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65:651–662PubMedCrossRefGoogle Scholar
  67. Kino T, Pavlakis GN (2004) Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1. DNA Cell Biol 23:193–205PubMedCrossRefGoogle Scholar
  68. Kino T, De Martino MU, Charmandari E, Ichijo T, Outas T, Chrousos GP (2005a) HIV-1 accessory protein Vpr inhibits the effect of insulin on the Foxo subfamily of forkhead transcription factors by interfering with their binding to 14-3-3 proteins: potential clinical implications regarding the insulin resistance of HIV-1-infected patients. Diabetes 54:23–31PubMedCrossRefGoogle Scholar
  69. Kino T, Gragerov A, Valentin A, Tsopanomihalou M, Ilyina-Gragerova G, Erwin-Cohen R, Chrousos GP, Pavlakis GN (2005b) Vpr protein of human immunodeficiency virus type 1 binds to 14-3-3 proteins and facilitates complex formation with Cdc25C: implications for cell cycle arrest. J Virol 79:2780–2787PubMedCrossRefGoogle Scholar
  70. Kogan M, Rappaport J (2011) HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention. Retrovirology 8:25PubMedCrossRefGoogle Scholar
  71. Lee SK, Park SO, Joe CO, Kim YS (2007) Interaction of HCV core protein with 14-3-3epsilon protein releases Bax to activate apoptosis. Biochem Biophys Res Commun 352:756–762PubMedCrossRefGoogle Scholar
  72. Letendre S, Paulino AD, Rockenstein E, Adame A, Crews L, Cherner M, Heaton R, Ellis R, Everall IP, Grant I, Masliah E (2007) Pathogenesis of hepatitis C virus coinfection in the brains of patients infected with HIV. J Infect Dis 196:361–370PubMedCrossRefGoogle Scholar
  73. Lipton SA (1992a) Models of neuronal injury in AIDS: another role for the NMDA receptor? Trends Neurosci 15:75–79PubMedCrossRefGoogle Scholar
  74. Lipton SA (1992b) Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120. Neuroreport 3:913–915PubMedCrossRefGoogle Scholar
  75. Liu J, Zhou G, Ji W, Li J, Li T, Wang T, Li Y, Zeng Z, Hu Z, Zheng L, Ji J, Wang Y, Wei Z, Feng G, He L, Shi Y (2011) No association of the YWHAE gene with schizophrenia, major depressive disorder or bipolar disorder in the Han Chinese population. Behav Genet 41:557–564PubMedCrossRefGoogle Scholar
  76. Malim MH, Emerman M (2008) HIV-1 accessory proteins—ensuring viral survival in a hostile environment. Cell Host Microbe 3:388–398PubMedCrossRefGoogle Scholar
  77. Martin H, Rostas J, Patel Y, Aitken A (1994) Subcellular localisation of 14-3-3 isoforms in rat brain using specific antibodies. J Neurochem 63:2259–2265PubMedCrossRefGoogle Scholar
  78. Mathie A, Rees KA, El Hachmane MF, Veale EL (2010) Trafficking of neuronal two pore domain potassium channels. Curr Neuropharmacol 8:276–286PubMedCrossRefGoogle Scholar
  79. Matsuda N, Tanaka H, Yamazaki S, Suzuki J, Tanaka K, Yamada T, Masuda M (2006) HIV-1 Vpr induces G2 cell cycle arrest in fission yeast associated with Rad24/14-3-3-dependent, Chk1/Cds1-independent Wee1 upregulation. Microbes Infect 8:2736–2744PubMedCrossRefGoogle Scholar
  80. McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, Sacktor N (2003) Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol 9:205–221PubMedGoogle Scholar
  81. Meller N, Liu YC, Collins TL, Bonnefoy-Berard N, Baier G, Isakov N, Altman A (1996) Direct interaction between protein kinase C theta (PKC theta) and 14-3-3 tau in T cells: 14-3-3 overexpression results in inhibition of PKC theta translocation and function. Mol Cell Biol 16:5782–5791PubMedGoogle Scholar
  82. Meller N, Altman A, Isakov N (1998) New perspectives on PKCtheta, a member of the novel subfamily of protein kinase C. Stem Cells 16:178–192PubMedCrossRefGoogle Scholar
  83. Mignon-Ravix C, Cacciagli P, El-Waly B, Moncla A, Milh M, Girard N, Chabrol B, Philip N, Villard L (2010) Deletion of YWHAE in a patient with periventricular heterotopias and pronounced corpus callosum hypoplasia. J Med Genet 47:132–136PubMedCrossRefGoogle Scholar
  84. Miller RF, Green AJ, Giovannoni G, Thompson EJ (2000) Detection of 14-3-3 brain protein in cerebrospinal fluid of HIV infected patients. Sex Transm Infect 76:408PubMedCrossRefGoogle Scholar
  85. Moens LN, De Rijk P, Reumers J, Van den Bossche MJ, Glassee W, De Zutter S, Lenaerts AS, Nordin A, Nilsson LG, Medina Castello I, Norrback KF, Goossens D, Van Steen K, Adolfsson R, Del-Favero J (2011) Sequencing of DISC1 pathway genes reveals increased burden of rare missense variants in schizophrenia patients from a northern Swedish population. PLoS One 6:e23450PubMedCrossRefGoogle Scholar
  86. Moore BW, Perez VJ (1967) Physiological and biochemical aspects of nervous integration. Prentice-Hall, New YorkGoogle Scholar
  87. Muslin AJ, Xing H (2000) 14-3-3 proteins: regulation of subcellular localization by molecular interference. Cell Signal 12:703–709PubMedCrossRefGoogle Scholar
  88. Nakamura H, Aoki H, Hino O, Moriyama M (2011) HCV core protein promotes heparin binding EGF-like growth factor expression and activates Akt. Hepatol Res 41:455–462PubMedCrossRefGoogle Scholar
  89. Nakamuta S, Endo H, Higashi Y, Kousaka A, Yamada H, Yano M, Kido H (2008) Human immunodeficiency virus type 1 gp120-mediated disruption of tight junction proteins by induction of proteasome-mediated degradation of zonula occludens-1 and -2 in human brain microvascular endothelial cells. J Neurovirol 14:186–195PubMedCrossRefGoogle Scholar
  90. Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J (2008) Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20:25–31PubMedCrossRefGoogle Scholar
  91. Obsil T, Obsilova V (2011) Structural basis of 14-3-3 protein functions. Semin Cell Dev BiolGoogle Scholar
  92. Okamoto Y, Shikano S (2011) Phosphorylation-dependent C-terminal binding of 14-3-3 proteins promotes cell surface expression of HIV co-receptor GPR15. J Biol Chem 286:7171–7181PubMedCrossRefGoogle Scholar
  93. Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S (2002) Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt–Jakob disease. Neurology 58:192–197PubMedCrossRefGoogle Scholar
  94. Peoc'h K, Delasnerie-Laupretre N, Beaudry P, Laplanche JL (2006) Diagnostic value of CSF 14-3-3 detection in sporadic CJD diagnosis according to the age of the patient. Eur J Neurol 13:427–428PubMedCrossRefGoogle Scholar
  95. Plant LD, Rajan S, Goldstein SA (2005) K2P channels and their protein partners. Curr Opin Neurobiol 15:326–333PubMedCrossRefGoogle Scholar
  96. Poser S, Mollenhauer B, Kraubeta A, Zerr I, Steinhoff BJ, Schroeter A, Finkenstaedt M, Schulz-Schaeffer WJ, Kretzschmar HA, Felgenhauer K (1999) How to improve the clinical diagnosis of Creutzfeldt–Jakob disease. Brain 122(Pt 12):2345–2351PubMedCrossRefGoogle Scholar
  97. Rittinger K, Budman J, Xu J, Volinia S, Cantley LC, Smerdon SJ, Gamblin SJ, Yaffe MB (1999) Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol Cell 4:153–166PubMedCrossRefGoogle Scholar
  98. Saiz A, Graus F, Dalmau J, Pifarre A, Marin C, Tolosa E (1999) Detection of 14-3-3 brain protein in the cerebrospinal fluid of patients with paraneoplastic neurological disorders. Ann Neurol 46:774–777CrossRefGoogle Scholar
  99. Sanchez-Valle R, Saiz A, Graus F (2002) 14-3-3 Protein isoforms and atypical patterns of the 14-3-3 assay in the diagnosis of Creutzfeldt–Jakob disease. Neurosci Lett 320:69–72PubMedCrossRefGoogle Scholar
  100. Shi B, De Girolami U, He J, Wang S, Lorenzo A, Busciglio J, Gabuzda D (1996) Apoptosis induced by HIV-1 infection of the central nervous system. J Clin Invest 98:1979–1990PubMedCrossRefGoogle Scholar
  101. Shikano S, Coblitz B, Sun H, Li M (2005) Genetic isolation of transport signals directing cell surface expression. Nat Cell Biol 7:985–992PubMedCrossRefGoogle Scholar
  102. Shimojima K, Sugiura C, Takahashi H, Ikegami M, Takahashi Y, Ohno K, Matsuo M, Saito K, Yamamoto T (2011) Genomic copy number variations at 17p13.3 and epileptogenesis. Epilepsy Res 89:303–309CrossRefGoogle Scholar
  103. Smith BL, Krushelnycky BW, Mochly-Rosen D, Berg P (1996) The HIV nef protein associates with protein kinase C theta. J Biol Chem 271:16753–16757PubMedCrossRefGoogle Scholar
  104. Spalice A, Parisi P, Nicita F, Pizzardi G, Del Balzo F, Iannetti P (2009) Neuronal migration disorders: clinical, neuroradiologic and genetics aspects. Acta Paediatr 98:421–433PubMedCrossRefGoogle Scholar
  105. Steinacker P, Aitken A, Otto M (2011) 14-3-3 proteins in neurodegeneration. Semin Cell Dev BiolGoogle Scholar
  106. Stewart SA, Poon B, Jowett JB, Chen IS (1997) Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest. J Virol 71:5579–5592PubMedGoogle Scholar
  107. Stewart SA, Poon B, Song JY, Chen IS (2000) Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation. J Virol 74:3105–3111PubMedCrossRefGoogle Scholar
  108. Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR (2011) Breaking down the barrier: the effects of HIV-1 on the blood-brain barrier. Brain Res 1399:96–115PubMedCrossRefGoogle Scholar
  109. Takahashi Y (2003) The 14-3-3 proteins: gene, gene expression, and function. Neurochem Res 28:1265–1273PubMedCrossRefGoogle Scholar
  110. Takahashi H, Iwata T, Kitagawa Y, Takahashi RH, Sato Y, Wakabayashi H, Takashima M, Kido H, Nagashima K, Kenney K, Gibbs CJ Jr, Kurata T (1999) Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt–Jakob disease. Clin Diagn Lab Immunol 6:983–985PubMedGoogle Scholar
  111. Tenney JR, Hopkin RJ, Schapiro MB (2011) Deletion of 14-3-3{varepsilon} and CRK: a clinical syndrome with macrocephaly, developmental delay, and generalized epilepsy. J Child Neurol 26:223–227PubMedCrossRefGoogle Scholar
  112. Thomson RB Jr, Bertram H (2001) Laboratory diagnosis of central nervous system infections. Infect Dis Clin North Am 15:1047–1071PubMedCrossRefGoogle Scholar
  113. Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 367:188–193PubMedCrossRefGoogle Scholar
  114. Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A (2003) 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller–Dieker syndrome. Nat Genet 34:274–285PubMedCrossRefGoogle Scholar
  115. Tschampa HJ, Neumann M, Zerr I, Henkel K, Schroter A, Schulz-Schaeffer WJ, Steinhoff BJ, Kretzschmar HA, Poser S (2001) Patients with Alzheimer's disease and dementia with Lewy bodies mistaken for Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 71:33–39PubMedCrossRefGoogle Scholar
  116. Tyson JJ, Csikasz-Nagy A, Novak B (2002) The dynamics of cell cycle regulation. Bioessays 24:1095–1109PubMedCrossRefGoogle Scholar
  117. Ullrich CK, Groopman JE, Ganju RK (2000) HIV-1 gp120- and gp160-induced apoptosis in cultured endothelial cells is mediated by caspases. Blood 96:1438–1442PubMedGoogle Scholar
  118. Unutmaz D, KewalRamani VN, Littman DR (1998) G protein-coupled receptors in HIV and SIV entry: new perspectives on lentivirus-host interactions and on the utility of animal models. Semin Immunol 10:225–236PubMedCrossRefGoogle Scholar
  119. Ushijima H, Nishio O, Klocking R, Perovic S, Muller WE (1995) Exposure to gp120 of HIV-1 induces an increased release of arachidonic acid in rat primary neuronal cell culture followed by NMDA receptor-mediated neurotoxicity. Eur J Neurosci 7:1353–1359PubMedCrossRefGoogle Scholar
  120. Valcour V, Sithinamsuwan P, Letendre S, Ances B (2011) Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep 8:54–61PubMedCrossRefGoogle Scholar
  121. van Heusden GP (2005) 14-3-3 proteins: regulators of numerous eukaryotic proteins. IUBMB Life 57:623–629PubMedCrossRefGoogle Scholar
  122. VanGuilder HD, Farley JA, Yan H, Van Kirk CA, Mitschelen M, Sonntag WE, Freeman WM (2011) Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline. Neurobiol Dis 43:201–212PubMedCrossRefGoogle Scholar
  123. Vodicka MA, Koepp DM, Silver PA, Emerman M (1998) HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection. Genes Dev 12:175–185PubMedCrossRefGoogle Scholar
  124. Wakabayashi H, Yano M, Tachikawa N, Oka S, Maeda M, Kido H (2001) Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction. Clin Chim Acta 312:97–105PubMedCrossRefGoogle Scholar
  125. Wang W, Shakes DC (1996) Molecular evolution of the 14-3-3 protein family. J Mol Evol 43:384–398PubMedCrossRefGoogle Scholar
  126. Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K (1995) Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. J Biol Chem 270:4854–4860PubMedCrossRefGoogle Scholar
  127. Wang Y, Jacobs C, Hook KE, Duan H, Booher RN, Sun Y (2000) Binding of 14-3-3beta to the carboxyl terminus of Wee1 increases Wee1 stability, kinase activity, and G2-M cell population. Cell Growth Differ 11:211–219PubMedGoogle Scholar
  128. Watanabe M, Isobe T, Okuyama T, Ichimura T, Kuwano R, Takahashi Y, Kondo H (1991) Molecular cloning of cDNA to rat 14-3-3 eta chain polypeptide and the neuronal expression of the mRNA in the central nervous system. Brain Res Mol Brain Res 10:151–158PubMedCrossRefGoogle Scholar
  129. Wiltfang J, Otto M, Baxter HC, Bodemer M, Steinacker P, Bahn E, Zerr I, Kornhuber J, Kretzschmar HA, Poser S, Ruther E, Aitken A (1999) Isoform pattern of 14-3-3 proteins in the cerebrospinal fluid of patients with Creutzfeldt–Jakob disease. J Neurochem 73:2485–2490PubMedCrossRefGoogle Scholar
  130. Won J, Kim DY, La M, Kim D, Meadows GG, Joe CO (2003) Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis. J Biol Chem 278:19347–19351PubMedCrossRefGoogle Scholar
  131. Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, Gamblin SJ (1995) Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature 376:188–191PubMedCrossRefGoogle Scholar
  132. Yaffe MB (2002) How do 14-3-3 proteins work? Gatekeeper phosphorylation and the molecular anvil hypothesis. FEBS Lett 513:53–57PubMedCrossRefGoogle Scholar
  133. Yanagi M, Shirakawa O, Kitamura N, Okamura K, Sakurai K, Nishiguchi N, Hashimoto T, Nushida H, Ueno Y, Kanbe D, Kawamura M, Araki K, Nawa H, Maeda K (2005) Association of 14-3-3 epsilon gene haplotype with completed suicide in Japanese. J Hum Genet 50:210–216PubMedCrossRefGoogle Scholar
  134. Yano M, Nakamuta S, Shiota M, Endo H, Kido H (2007) Gatekeeper role of 14-3-3tau protein in HIV-1 gp120-mediated apoptosis of human endothelial cells by inactivation of Bad. AIDS 21:911–920PubMedCrossRefGoogle Scholar
  135. Yingling J, Toyo-Oka K, Wynshaw-Boris A (2003) Miller–Dieker syndrome: analysis of a human contiguous gene syndrome in the mouse. Am J Hum Genet 73:475–488PubMedCrossRefGoogle Scholar
  136. Zerr I, Poser S (2002) Clinical diagnosis and differential diagnosis of CJD and vCJD. With special emphasis on laboratory tests. APMIS 110:88–98PubMedCrossRefGoogle Scholar
  137. Zerr I, Pocchiari M, Collins S, Brandel JP, de Pedro Cuesta J, Knight RS, Bernheimer H, Cardone F, Delasnerie-Laupretre N, Cuadrado Corrales N, Ladogana A, Bodemer M, Fletcher A, Awan T, Ruiz Bremon A, Budka H, Laplanche JL, Will RG, Poser S (2000a) Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease. Neurology 55:811–815PubMedCrossRefGoogle Scholar
  138. Zerr I, Schulz-Schaeffer WJ, Giese A, Bodemer M, Schroter A, Henkel K, Tschampa HJ, Windl O, Pfahlberg A, Steinhoff BJ, Gefeller O, Kretzschmar HA, Poser S (2000b) Current clinical diagnosis in Creutzfeldt–Jakob disease: identification of uncommon variants. Ann Neurol 48:323–329PubMedCrossRefGoogle Scholar
  139. Zhao LJ, Mukherjee S, Narayan O (1994a) Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. J Biol Chem 269:15577–15582PubMedGoogle Scholar
  140. Zhao LJ, Wang L, Mukherjee S, Narayan O (1994b) Biochemical mechanism of HIV-1 Vpr function. Oligomerization mediated by the N-terminal domain. J Biol Chem 269:32131–32137PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2012

Authors and Affiliations

  • Diana Morales
    • 1
  • Efthimios C. M. Skoulakis
    • 3
  • Summer F. Acevedo
    • 1
    • 2
  1. 1.Department of Physiology, Pharmacology, and ToxicologyPonce School of Medicine and Health SciencesPoncePuerto Rico
  2. 2.Psychology ProgramPonce School of Medicine and Health SciencesPoncePuerto Rico
  3. 3.Biomedical Sciences Research Center Alexander FlemingVariGreece

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