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Journal of NeuroVirology

, Volume 25, Issue 5, pp 648–660 | Cite as

HIV and Alzheimer’s disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein

  • Alina Hategan
  • Eliezer Masliah
  • Avindra NathEmail author
Article

Abstract

In patients infected with the human immunodeficiency virus (HIV), the HIV-Tat protein may be continually produced despite adequate antiretroviral therapy. As the HIV-infected population is aging, it is becoming increasingly important to understand how HIV-Tat may interact with proteins such as amyloid β and Tau which accumulate in the aging brain and eventually result in Alzheimer’s disease. In this review, we examine the in vivo data from HIV-infected patients and animal models and the in vitro experiments that show how protein complexes between HIV-Tat and amyloid β occur through novel protein-protein interactions and how HIV-Tat may influence the pathways for amyloid β production, degradation, phagocytosis, and transport. HIV-Tat may also induce Tau phosphorylation through a cascade of cellular processes that lead to the formation of neurofibrillary tangles, another hallmark of Alzheimer’s disease. We also identify gaps in knowledge and future directions for research. Available evidence suggests that HIV-Tat may accelerate Alzheimer-like pathology in patients with HIV infection which cannot be impacted by current antiretroviral therapy.

Keywords

Alzheimer’s disease AIDS Dementia Neurodegeneration HIV-Tat Protein misfolding Aggregation Brain 

Notes

References

  1. Achim CL, Adame A, Dumaop W, Everall IP, Masliah E, Neurobehavioral Research Center (2009) Increased accumulation of intraneuronal amyloid beta in HIV-infected patients. J NeuroImmune Pharmacol 4(2):190–199PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO (2010) Structural conversion of neurotoxic amyloid-beta (1-42) oligomers to fibrils. Nat Struct Mol Biol 17(5):561–567PubMedPubMedCentralCrossRefGoogle Scholar
  3. Aksenov MY, Aksenova MV, Mactutus CF, Booze RM (2009) Attenuated neurotoxicity of the transactivation-defective HIV-1 Tat protein in hippocampal cell cultures. Exp Neurol 219(2):586–590PubMedPubMedCentralCrossRefGoogle Scholar
  4. Aksenov MY, Aksenova MV, Mactutus CF, Booze RM (2010) HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures. Neurosci Lett 475(3):174–178PubMedPubMedCentralCrossRefGoogle Scholar
  5. Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K (2001) Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc Natl Acad Sci U S A 98(12):6923–6928PubMedPubMedCentralCrossRefGoogle Scholar
  6. András IE, Toborek M (2011) HIV-1-induced alterations of claudin-5 expression at the blood-brain barrier level. Methods Mol Biol 762:355–370PubMedPubMedCentralCrossRefGoogle Scholar
  7. András IE, Toborek M (2013) Amyloid beta accumulation in HIV-1-infected brain: the role of the blood brain barrier. IUBMB Life 65(1):43–49PubMedCrossRefPubMedCentralGoogle Scholar
  8. András IE, Pu H, Deli MA, Nath A, Hennig B, Toborek M (2003) HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. J Neurosci Res 74(2):255–265PubMedCrossRefPubMedCentralGoogle Scholar
  9. András IE, Pu H, Tian J, Deli MA, András IE, Pu H, Tian J, Deli MA, Nath A, Hennig B, Toborek M (2005) Signaling mechanisms of HIV-1 Tat-induced alterations of claudin-5 expression in brain endothelial cells. J Cereb Blood Flow Metab 25(9):1159–1170PubMedCrossRefPubMedCentralGoogle Scholar
  10. András IE, Rha G, Huang W, Eum S, Couraud PO, Romero IA, Hennig B, Toborek M (2008) Simvastatin protects against amyloid beta and HIV-1 Tat-induced promoter activities of inflammatory genes in brain endothelial cells. Mol Pharmacol 73(5):1424–1433PubMedPubMedCentralCrossRefGoogle Scholar
  11. András IE, Eum SY, Huang W, Zhong Y, Hennig B, Toborek M (2010) HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin. Mol Cell Neurosci 43(2):232–243PubMedCrossRefPubMedCentralGoogle Scholar
  12. Avraham HK, Jiang S, Lee TH, Prakash O, Avraham S (2004) HIV-1 Tat-mediated effects on focal adhesion assembly and permeability in brain microvascular endothelial cells. J Immunol 173:6228–6233PubMedCrossRefPubMedCentralGoogle Scholar
  13. Bagashev A, Sawaya BE (2013) Roles and functions of HIV-1 Tat protein in the CNS: an overview. Virol J 10:358–378PubMedPubMedCentralCrossRefGoogle Scholar
  14. Ball KA, Wemmer DE, Head-Gordon T (2014) Comparison of structure determination methods for intrinsically disordered amyloid-β peptides. J Phys Chem B 118:6405–6416PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G (1999) It all sticks together- -the APP-related family of proteins and Alzheimer’s disease. Mol Psychiatry 4(6):524–528PubMedCrossRefPubMedCentralGoogle Scholar
  16. Becker JT, Lopez OL, Dew MA, Aizenstein HJ (2004) Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS 18:S11–S18CrossRefGoogle Scholar
  17. Ben-Dov N, Korenstein R (2015) The uptake of HIV Tat peptide proceeds via two pathways which differ from macropinocytosis. Biochim Biophys Acta 1848(3):869–877PubMedCrossRefPubMedCentralGoogle Scholar
  18. Bright NA, Davis LJ, Luzio JP (2016) Endolysosomes are the principal intracellular sites of acid hydrolase activity. Curr Biol 26(17):2233–2245PubMedPubMedCentralCrossRefGoogle Scholar
  19. Brooks H, Lebleu B, Vivès E (2005) Tat peptide-mediated cellular delivery: back to basics. Adv Drug Deliv Rev 57(4):559–577PubMedCrossRefPubMedCentralGoogle Scholar
  20. Bu XL, Xiang Y, Jin WS, Wang J, Shen LL, Huang ZL, Zhang K, Liu YH, Zeng F, Liu JH, Sun HL, Zhuang ZQ, Chen SH, Yao XQ, Giunta B, Shan YC, Tan J, Chen XW, Dong ZF, Zhou HD, Zhou XF, Song W, Wang YJ (2018) Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies. Mol Psychiatry 9:1–9Google Scholar
  21. Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157(1):277–286PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chen L, Choi JJ, Choi YJ, Hennig B, Toborek M (2012) HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits. Neurobiol Aging 33(8):1579–1590PubMedCrossRefPubMedCentralGoogle Scholar
  23. Chen X, Hui L, Geiger NH, Haughey NJ, Geiger JD (2013) Endolysosome involvement in HIV-1 transactivator protein-induced neuronal amyloid beta production. Neurobiol Aging 34(10):2370–2378PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chen Y, Huang W, Jiang W, Wu X, Ye B, Zhou X (2016) HIV-1 Tat regulates occludin and Aβ transfer receptor expression in brain endothelial cells via Rho/ROCK signaling pathway. Oxidative Med Cell Longev 2016:4196572Google Scholar
  25. Chiti F, Webster P, Taddei N, Clark A, Stefani M, Ramponi G, Dobson CM (1999) Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc Natl Acad Sci U S A 96(7):3590–3594PubMedPubMedCentralCrossRefGoogle Scholar
  26. Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S, Griffin RG (2016) Atomic resolution structure of monomorphic Aβ 42 amyloid fibrils. J Am Chem Soc 138(30):9663–9674PubMedPubMedCentralCrossRefGoogle Scholar
  27. Conchillo-Solé O, de Groot NS, Avilés FX, Vendrell J, Daura X, Ventura S (2007) AGGRESCAN: a server for the prediction and evaluation of “hot spots” of aggregation in polypeptides. BMC Bioinformatics 8:65PubMedPubMedCentralCrossRefGoogle Scholar
  28. Daily A, Nath A, Hersh L (2006) Tat peptides inhibit neprilysin. J Neuro-Oncol 12:153–160Google Scholar
  29. de Almeida SM, Ribeiro CE, Rotta I, Piovesan M, Tang B, Vaida F, Raboni SM, Letendre S, Potter M, Batistela Fernandes MS, Ellis RJ, HIV Neurobehavioral Research Center (HNRC) Group (2018) Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C. J Neuro-Oncol 24(1):28–40Google Scholar
  30. de Groot NS, Castillo V, Graña-Montes R, Ventura S (2012) AGGRESCAN: method, application, and perspectives for drug design. In: Baron R (ed) Computational drug discovery and design. Methods in molecular biology (methods and protocols), vol 819. Springer, New YorkGoogle Scholar
  31. Deane R, Wu Z, Zlokovic BV (2004) RAGE (yin) versus LRP (yang) balance regulates Alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier. Stroke 35(11 Suppl 1):2628–2631PubMedCrossRefGoogle Scholar
  32. Debaisieux S, Rayne F, Yezid H, Beaumelle B (2012) The ins and outs of HIV-1 Tat. Traffic 13:355–363PubMedCrossRefGoogle Scholar
  33. Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Aussio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001) Intrinsically disordered protein. J Mol Graph Model 19:26–59PubMedPubMedCentralCrossRefGoogle Scholar
  34. Ehehalt R, Keller P, Haass C, Thiele C, Simons K (2003) Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 160:113–123PubMedPubMedCentralCrossRefGoogle Scholar
  35. Esiri MM, Biddolph SC, Morris CS (1998) Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry 65:29–33PubMedPubMedCentralCrossRefGoogle Scholar
  36. Everall IP, Heaton RK, Marcotte TD, Ellis RJ, McCutchan JA, Atkinson JH, Grant I, Mallory M, Masliah E (1999) Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. HNRC Group. HIV Neurobehavioral Research Center. Brain Pathol 9:209–217PubMedCrossRefGoogle Scholar
  37. Ferrari A, Pellegrini V, Arcangeli C, Fittipaldi A, Giacca M, Beltram F (2003) Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time. Mol Ther 8(2):284–294PubMedCrossRefGoogle Scholar
  38. Ferrell D, Giunta B (2014) The impact of HIV-1 on neurogenesis: implications for HAND. Cell Mol Life Sci 71(22):4387–4392PubMedPubMedCentralCrossRefGoogle Scholar
  39. Fields JA, Dumaop W, Crews L, Adame A, Spencer B, Metcalf J, He J, Rockenstein E, Masliah E (2015a) Mechanisms of HIV-1 Tat neurotoxicity via CDK5 translocation and hyper-activation: role in HIV-associated neurocognitive disorders. Curr HIV Res 13(1):43–54PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fields J, Dumaop W, Eleuteri S, Campos S, Serger E, Trejo M, Kosberg K, Adame A, Spencer B, Rockenstein E, He JJ, Masliah E (2015b) HIV-1 Tat alters neuronal autophagy by modulating autophagosome fusion to the lysosome: implications for HIV-associated neurocognitive disorders. J Neurosci 35(5):1921–1938PubMedPubMedCentralCrossRefGoogle Scholar
  41. Fittipaldi A, Ferrari A, Zoppé M, Arcangeli C, Pellegrini V, Beltram F, Giacca M (2003) Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J Biol Chem 278(36):34141–34149PubMedCrossRefGoogle Scholar
  42. Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547(7662):185–190PubMedPubMedCentralCrossRefGoogle Scholar
  43. Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55(6):1189–1193PubMedCrossRefGoogle Scholar
  44. Fraser PE, Nguyen JT, Inouye H, Surewicz WK, Selkoe DJ, Podlisny MB, Kirschner DA (1992) Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein. Biochemistry 31(44):10716–10723PubMedCrossRefGoogle Scholar
  45. Garner E, Romero P, Dunker AK, Brown C, Obradovic Z (1999) Predicting binding regions within disordered proteins. Genome Inform 10:41–50Google Scholar
  46. Giunta B, Zhou Y, Hou H, Rrapo E, Fernandez F et al (2008) HIV-1 Tat inhibits microglial phagocytosis of Abeta peptide. Int J Clin Exp Pathol 1:260–275PubMedPubMedCentralGoogle Scholar
  47. Giunta B, Hou H, Zhu Y, Rrapo E, Tian J et al (2009) HIV-1 Tat contributes to Alzheimer’s disease-like pathology in PSAPP mice. Int J Clin Exp Pathol 2:433–443PubMedPubMedCentralGoogle Scholar
  48. Giunta B, Ehrhart J, Obregon DF, Lam L, Le L, Jin J, Fernandez F, Tan J, Shytle RD (2011) Antiretroviral medications disrupt microglial phagocytosis of β-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders. Mol Brain 4(1):23PubMedPubMedCentralCrossRefGoogle Scholar
  49. Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL (2005) Brain deposition of β-amyloid is a common pathologic feature in HIV positive patients. AIDS 19:407–411CrossRefGoogle Scholar
  50. Guo X, Kameoka M, Wei X, Roques B, Gotte M, Liang C, Wainberg MA (2003) Suppression of an intrinsic strand transfer activity of HIV-1 Tat protein by its second-exon sequences. Virology 307:154–163PubMedCrossRefGoogle Scholar
  51. Halverson K, Fraser PE, Kirschner DA, Lansbury PT Jr (1990) Molecular determinants of amyloid deposition in Alzheimer’s disease: conformational studies of synthetic beta-protein fragments. Biochemistry 29(11):2639–2644PubMedCrossRefGoogle Scholar
  52. Hategan A, Bianchet MA, Steiner J, Karnaukhova E, Masliah E, Fields A, Lee MH, Dickens AM, Haughey N, Dimitriadis EK, Nath A (2017) HIV Tat protein and amyloid-β peptide form multifibrillar structures that cause neurotoxicity. Nat Struct Mol Biol 24(4):379–386PubMedPubMedCentralCrossRefGoogle Scholar
  53. Hayashi K, Pu H, Tian J, Andras IE, Lee YW, Hennig B, Toborek M (2005) HIV-Tat protein induces P-glycoprotein expression in brain microvascular endothelial cells. J Neurochem 93(5):1231–1241PubMedCrossRefGoogle Scholar
  54. Hayashi K, Pu H, Andras IE, Eum SY, Yamauchi A, Hennig B, Toborek M (2006) HIVTAT protein upregulates expression of multidrug resistance protein 1 in the blood-brain barrier. J Cereb Blood Flow Metab 26(8):1052–1065PubMedCrossRefGoogle Scholar
  55. Hayman M, Arbuthnott G, Harkiss G, Brace H, Filippi P, Philippon V, Thomson D, Vigne R, Wright A (1993) Neurotoxicity of peptide analogues of the transactivating protein Tat from Maedi-Visna virus and human immunodeficiency virus. Neuroscience 53:1–6PubMedCrossRefGoogle Scholar
  56. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, CHARTER Group, HNRC Group (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neuro-Oncol 17(1):3–16Google Scholar
  57. Hellmuth J, Milanini B, Masliah E, Tartaglia MC, Dunlop MB, Moore DJ, Javandel S, DeVaughn S, Valcour V (2018) A neuropathologic diagnosis of Alzheimer’s disease in an older adult with HIV-associated neurocognitive disorder. Neurocase 4:213–219CrossRefGoogle Scholar
  58. Huang W, Chen L, Zhang B, Park M, Toborek M (2014) PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced in MMP-9-deficient mice. J Cereb Blood Flow Metab 34(4):646–653PubMedPubMedCentralCrossRefGoogle Scholar
  59. Hui L, Chen X, Haughey NJ, Geiger JD (2012) Role of endolysosomes in HIV-1 Tat-induced neurotoxicity. ASN Neuro 4(4):243–252PubMedCrossRefGoogle Scholar
  60. Iqbal K, Liu F, Gong CX, Grundke-Iqbal I (2010) Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res 7(8):656–664PubMedPubMedCentralCrossRefGoogle Scholar
  61. Iwata N, Tsubuki S, Takaki Y, Shirotani K, Lu B, Gerard NP, Gerard C, Hama E, Lee HJ, Saido TC (2001) Metabolic regulation of brain Abeta by neprilysin. Science 292(5521):1550–1552PubMedCrossRefGoogle Scholar
  62. Jaeger LB, Dohgu S, Hwang MC, Farr SA, Murphy MP, Fleegal-DeMotta MA, Lynch JL, Robinson SM, Niehoff ML, Johnson SN, Kumar VB, Banks WA (2009) Testing the neurovascular hypothesis of Alzheimer’s disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition. J Alzheimers Dis 17(3):553–570PubMedPubMedCentralCrossRefGoogle Scholar
  63. Jeang KT, Xiao H, Rich EA (1999) Multifaceted activities of the HIV-1 transactivator of transcription. Tat J Biol Chem 274:28837–28840PubMedCrossRefGoogle Scholar
  64. Jiang W, Huang W, Chen Y, Zou M, Peng D, Chen D (2017) HIV-1 Transactivator protein induces ZO-1 and neprilysin dysfunction in brain endothelial cells via the Ras signaling pathway. Oxidative Med Cell Longev 2017:3160360Google Scholar
  65. Johnson TP, Patel K, Johnson KR, Maric D, Calabresi PA, Hasbun R, Nath A (2013) Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proc Natl Acad Sci U S A 10(33):13588–13593CrossRefGoogle Scholar
  66. Kadri F, Pacifici M, Wilk A, Parker-Struckhoff A, Del Valle L, Hauser KF, Knapp PE, Parsons C, Jeansonne D, Lassak A, Peruzzi F (2015) HIV-1-Tat protein inhibits SC35-mediated Tau exon 10 inclusion through up-regulation of DYRK1A kinase. J Biol Chem 290(52):30931–30946PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300:486–489PubMedCrossRefGoogle Scholar
  68. Khan MB, Lang MJ, Huang MB, Raymond A, Bond VC, Shiramizu B, Powell MD (2016) Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ_(1-42) secretion in SH-SY5Y neural cells. J Neuro-Oncol 2:179–190Google Scholar
  69. Kim J, Yoon JH, Kim YS (2013) HIV-1 Tat interacts with and regulates the localization and processing of amyloid precursor protein. PLoS One 8(11):e77972PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kodali R, Williams AD, Chemuru S, Wetzel R (2010) Abeta(1-40) forms five distinct amyloid structures whose β-sheet contents and fibril stabilities are correlated. J Mol Biol 401:503–517PubMedPubMedCentralCrossRefGoogle Scholar
  71. Koo EH, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuther K, Fischer P, Masters CL, Price DL (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci U S A 87:1561–1565PubMedPubMedCentralCrossRefGoogle Scholar
  72. Lansbury PT Jr (1999) Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc Natl Acad Sci U S A 96(7):3342–3344PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lee J, Retamal C, Cuitino L, Caruano-Yzermans A, Shin JE, van Kerkhof P, Marzolo MP, Bu G (2008) Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. J Biol Chem 283:11501–11508PubMedPubMedCentralCrossRefGoogle Scholar
  74. Li W, Li G, Steiner J, Nath A (2009) Role of tat protein in HIV neuropathogenesis. Neurotox Res 16(3):205–220PubMedCrossRefGoogle Scholar
  75. Li S, Hou H, Mori T, Sawmiller D, Smith A, Tian J, Wang Y, Giunta B, Sanberg PR, Zhang S, Tan J (2015) Swedish mutant APP-based BACE1 binding site peptide reduces APP β-cleavage and cerebral Aβ levels in Alzheimer’s mice. Sci Rep 5:11322PubMedPubMedCentralCrossRefGoogle Scholar
  76. Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6(12):1380–1387PubMedCrossRefGoogle Scholar
  77. Lu JX, Qiang W, Yau WM, Schwieters CD, Meredith SC, Tycko R (2013) Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue. Cell 154(6):1257–1268PubMedCrossRefGoogle Scholar
  78. Ma M, Nath A (1997) Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells. J Virol 71(3):2495–2499PubMedPubMedCentralGoogle Scholar
  79. Macchi S, Nifosì R, Signore G, Di Pietro S, Boccardi C, D'Autilia F, Beltram F, Cardarelli F (2017) Self-aggregation propensity of the Tat peptide revealed by UV-Vis, NMR and MD analyses. Phys Chem Chem Phys 19(35):23910–23914PubMedCrossRefGoogle Scholar
  80. Maragos WF, Tillman P, Jones M, Bruce-Keller AJ, Roth S, Bell JE, Nath A (2003) Neuronal injury in hippocampus with human immunodeficiency virus transactivating protein, Tat. Neuroscience 117:43–53PubMedCrossRefPubMedCentralGoogle Scholar
  81. Martínez-Bonet M, Muñoz-Fernández MÁ, Álvarez S (2018) HIV-1 increases extracellular amyloid-beta levels through neprilysin regulation in primary cultures of human astrocytes. J Cell Physiol.  https://doi.org/10.1002/jcp.26462
  82. Masliah E, Westland CE, Rockenstein EM, Abraham CR, Mallory M, Veinberg I, Sheldon E, Mucke L (1997) Amyloid precursor proteins protect neurons of transgenic mice against acute and chronic excitotoxic injuries in vivo. Neuroscience 78(1):135–146PubMedCrossRefPubMedCentralGoogle Scholar
  83. Mattson MP, Haughey NJ, Nath A (2005) Cell death in HIV dementia. Cell Death Differ Suppl 1:893–904CrossRefGoogle Scholar
  84. Mishra A, Gordon VD, Yang L, Coridan R, Wong GC (2008) HIV TAT forms pores in membranes by inducing saddle-splay curvature: potential role of bidentate hydrogen bonding. Angew Chem Int Ed Engl 47(16):2986–2989PubMedCrossRefPubMedCentralGoogle Scholar
  85. Moores B, Drolle E, Attwood SJ, Simons J, Leonenko Z (2011) Effect of surfaces on amyloid fibril formation. PLoS One 6:e25954PubMedPubMedCentralCrossRefGoogle Scholar
  86. Morgello S, Jacobs M, Murray J, Byrd D, Neibart E, Mintz L, Meloni G, Chon C, Crary J (2018) Alzheimer’s disease neuropathology may not predict functional impairment in HIV: a report of two individuals. J Neuro-Oncol 5:629–637Google Scholar
  87. Moss S, Subramanian V, Acharya KR (2018) High resolution crystal structure of substrate-free human neprilysin. J Struct Biol 204(1):19–25PubMedCrossRefPubMedCentralGoogle Scholar
  88. Nath A, Hersh LB (2005) Tat and amyloid: multiple interactions. AIDS 19(2):203–204PubMedCrossRefPubMedCentralGoogle Scholar
  89. Nath A, Steiner J (2014) Synaptodendritic injury with HIV-Tat protein: what is the therapeutic target? Exp Neurol 251:112–114PubMedCrossRefPubMedCentralGoogle Scholar
  90. Nath A, Psooy K, Martin C, Knudsen B, Magnuson DS, Haughey N, Geiger JD (1996) Identification of a human immunodeficiency virus type 1 Tat epitope that is neuroexcitatory and neurotoxic. J Virol 70(3):1475–1480PubMedPubMedCentralGoogle Scholar
  91. Nath A, Haughey NJ, Jones M, Anderson C, Bell JE, Geiger JD (2000) Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine. Ann Neurol 47(2):186–194PubMedCrossRefPubMedCentralGoogle Scholar
  92. Nguyen HD, Hall CK (2004) Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides. Proc Natl Acad Sci U S A 101(46):16180–16185PubMedPubMedCentralCrossRefGoogle Scholar
  93. O'Brien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204PubMedPubMedCentralCrossRefGoogle Scholar
  94. Paravastu AK, Leapman RD, Yau WM, Tycko R (2008) Molecular structural basis for polymorphism in Alzheimer’s β-amyloid fibrils. Proc Natl Acad Sci U S A 105(1834):9–18354Google Scholar
  95. Parthsarathy V, McClean PL, Hölscher C, Taylor M, Tinker C, Jones G, Kolosov O, Salvati E, Gregori M, Masserini M, Allsop D (2013) A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1∆E9 mouse model of Alzheimer’s disease. PLoS One 8(1):e54769PubMedPubMedCentralCrossRefGoogle Scholar
  96. Peng K, Vucetic S, Radivojac P, Brown CJ, Dunker AK, Obradovic Z (2005) Optimizing long intrinsic disorder predictors with protein evolutionary information. J Bioinforma Comput Biol 1:35–60CrossRefGoogle Scholar
  97. Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R (2005) Self-propagating, molecular-level polymorphism in Alzheimer’s β-amyloid fibrils. Science 307:262–265PubMedCrossRefPubMedCentralGoogle Scholar
  98. Potocky TB, Menon AK, Gellman SH (2003) Cytoplasmic and nuclear delivery of a TAT-derived peptide and a beta-peptide after endocytic uptake into HeLa cells. J Biol Chem 278(50):50188–50194PubMedCrossRefPubMedCentralGoogle Scholar
  99. Pu H, Tian J, Andras IE, Hayashi K, Flora G, Hennig B, Toborek M (2005) HIV-1 Tat protein-induced alterations of ZO-1 expression are mediated by redox-regulated ERK 1/2 activation. J Cereb Blood Flow Metab 25(10):1325–1335PubMedCrossRefPubMedCentralGoogle Scholar
  100. Pulliam L (2009) HIV regulation of amyloid beta production. J Neuroimmune Pharmacol 4(2):213–217PubMedCrossRefPubMedCentralGoogle Scholar
  101. Pulliam L, Sun B, Rempel H, Martinez PM, Hoekman JD, Rao RJ, Frey WH 2nd, Hanson LR (2007) Intranasal tat alters gene expression in the mouse brain. J NeuroImmune Pharmacol 2(1):87–92PubMedCrossRefPubMedCentralGoogle Scholar
  102. Pulliam L, Sun B, Mustapic M, Chawla S, Kapogiannis D (2019) Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer’s disease. J Neuro-Oncol.  https://doi.org/10.1007/s13365-018-0695-4
  103. Rahimian P, He JJ (2016) Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein. J Neuro-Oncol 6:774–788Google Scholar
  104. Rambaran RN, Serpell LC (2008) Amyloid fibrils: abnormal protein assembly. Prion 2(3):112–117PubMedPubMedCentralCrossRefGoogle Scholar
  105. Rempel HC, Pulliam L (2005) HIV-1Tat inhibits neprilysin and elevates amyloid beta. AIDS 19(2):127–135CrossRefGoogle Scholar
  106. Rockenstein E, Hansen LA, Mallory M, Trojanowski JQ, Galasko D, Masliah E (2001) Altered expression of the synuclein family mRNA in Lewy body and Alzheimer’s disease. Brain Res 914(1–2):48–56PubMedCrossRefPubMedCentralGoogle Scholar
  107. Rogers J, Lue LF (2001) Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer’s disease. Neurochem Int 39(5–6):333–340PubMedCrossRefPubMedCentralGoogle Scholar
  108. Rogers J, Strohmeyer R, Kovelowski CJ, Li R (2002) Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide. Glia 40(2):260–269PubMedCrossRefPubMedCentralGoogle Scholar
  109. Rossner S, Lange-Dohna C, Zeitschel U, Perez-Polo JR (2005) Alzheimer’s disease beta-secretase BACE1 is not a neuron-specific enzyme. J Neurochem 92(2):226–234PubMedCrossRefPubMedCentralGoogle Scholar
  110. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8(6):595–608PubMedPubMedCentralCrossRefGoogle Scholar
  111. Serpell LC (2000) Alzheimer’s amyloid fibrils: structure and assembly. Biochim Biophys Acta 1502(1):16–30PubMedCrossRefGoogle Scholar
  112. Shirotani K, Tsubuki S, Iwata N, Takaki Y, Harigaya W, Maruyama K, Kiryu-Seo S, Kiyama H, Iwata H, Tomita T, Iwatsubo T, Saido TC (2001) Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. J Biol Chem 276(24):21895–21901PubMedCrossRefGoogle Scholar
  113. Shojania S, O’Neil JD (2006) HIV-1 Tat is a natively unfolded protein: the solution conformation and dynamics of reduced HIV-1 Tat-(1-72) by NMR spectroscopy. J Biol Chem 281:8347–8356PubMedCrossRefGoogle Scholar
  114. Shojania S, O’Neil JD (2010) Intrinsic disorder and function of the HIV-1 Tat protein. Protein Pept Lett 17:999–1011PubMedCrossRefGoogle Scholar
  115. Sisodia SS, Koo EH, Beyreuther K, Unterbeck A, Price DL (1990) Evidence that beta –amyloid protein in Alzheimer’s disease is not derived by normal processing. Science 248:492–495PubMedCrossRefGoogle Scholar
  116. Smith SM, Pentlicky S, Klase Z, Singh M, Neuveut C, Lu CY, Reitz MS Jr, Yarchoan R, Marx PA, Jeang KT (2003) An in vivo replication-important function in the second coding exon of Tat is constrained against mutation despite cytotoxic T lymphocyte selection. J Biol Chem 278:44816–44825PubMedCrossRefGoogle Scholar
  117. Soliman ML, Geiger JD, Chen X (2017) Caffeine blocks HIV-1 Tat-induced amyloid beta production and Tau phosphorylation. J NeuroImmune Pharmacol 12(1):163–170PubMedCrossRefGoogle Scholar
  118. Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH (2010) Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature 465(7299):747–751PubMedPubMedCentralCrossRefGoogle Scholar
  119. Tyagi M, Rusnati M, Presta M, Giacca M (2001) Internalization of HIV-1 Tat requires cell surface heparan sulfate proteoglycans. J Biol Chem 276(5):3254–3261PubMedCrossRefGoogle Scholar
  120. Uversky VN (2002) Natively unfolded proteins: a point where biology waits for physics. Protein Sci 11:739–756PubMedPubMedCentralCrossRefGoogle Scholar
  121. Valcour VG, Shikuma CM, Watters MR, Sacktor NC (2004) Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms. AIDS 18:S79–S86PubMedPubMedCentralCrossRefGoogle Scholar
  122. Vendeville A, Rayne F, Bonhoure A, Bettache N, Montcourrier P, Beaumelle B (2004) HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses. Mol Biol Cell 15(5):2347–2360PubMedPubMedCentralCrossRefGoogle Scholar
  123. Wälti MA, Ravotti F, Arai H, Glabe CG, Wall JS, Böckmann A, Güntert P, Meier BH, Riek R (2016) Atomic-resolution structure of a disease-relevant Aβ (1-42) amyloid fibril. Proc Natl Acad Sci U S A 113(34):E4976–E4984PubMedPubMedCentralCrossRefGoogle Scholar
  124. Westendorp MO, Frank R, Ochsenbauer C, Stricker K, Dhein J, Walczak H, Debatin KM, Krammer PH (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375(6531):497–500PubMedCrossRefPubMedCentralGoogle Scholar
  125. Yezid H, Konate K, Debaisieux S, Bonhoure A, Beaumelle B (2009) Mechanism for HIV- 1 Tat insertion into the endosome membrane. J Biol Chem 284(34):22736–22746PubMedPubMedCentralCrossRefGoogle Scholar
  126. Zeitler M, Steringer JP, Müller HM, Mayer MP, Nickel W (2015) HIV-Tat protein forms phosphoinositide-dependent membrane pores implicated in unconventional protein secretion. J Biol Chem 290(36):21976–21984PubMedPubMedCentralCrossRefGoogle Scholar
  127. Zhao J, Paganini L, Mucke L, Gordon M, Refolo L, Carman M, Sinha S, Oltersdorf T, Lieberburg I, McConlogue L (1996) Beta-secretase processing of the beta-amyloid precursor protein in transgenic mice is efficient in neurons but inefficient in astrocytes. J Biol Chem 271(49):31407–31411PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  1. 1.Section of Infections of the Nervous System, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaUSA
  2. 2.Division of Neuroscience, National Institute of AgingNational Institutes of HealthBethesdaUSA

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