Cellular & molecular basis of HIV-associated neuropathogenesis

Indian Journal of Medical Research

Volumn 129, Issue 6, 2009, Pages 637-651

  Sharma, Deepak ^a   Bhattacharya, Jayanta ^a  

^a NATIONAL AIDS RESEARCH INSTITUTE   (India)

Author keywords

Apoptosis; Blood brain barrier; Chemokines; HIV associated dementia; Neuropathogenesis; Transcription factors

Indexed keywords

ARACHIDONIC ACID; CALCIUM ION; CELL ADHESION MOLECULE; CHEMOKINE; CHEMOKINE RECEPTOR CCR5; CYTOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GLUTAMIC ACID; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 1; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN; MATRIX METALLOPROTEINASE; MONOCYTE CHEMOTACTIC PROTEIN 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEF PROTEIN; NITRIC OXIDE; RANTES; TRANSACTIVATOR PROTEIN; TUMOR NECROSIS FACTOR; VIRUS ENVELOPE PROTEIN; VPR PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; APOPTOSIS; BLOOD BRAIN BARRIER; BRAIN INFECTION; CD4+ T LYMPHOCYTE; DISEASE ASSOCIATION; DISEASE COURSE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; LONG TERMINAL REPEAT; MACROPHAGE; MICROGLIA; MOLECULAR DYNAMICS; NEUROPATHOLOGY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SYNAPTIC TRANSMISSION; VIROGENESIS; VIRUS ENTRY; VIRUS REPLICATION;

AIDS DEMENTIA COMPLEX; ANIMALS; APOPTOSIS; BLOOD-BRAIN BARRIER; BRAIN; CELL MOVEMENT; CHEMOKINES; CYTOKINES; HIV INFECTIONS; HIV-1; HUMANS; INDIA; NEUROTRANSMITTER AGENTS; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 70349529794     PISSN: 09715916     EISSN: 09715916     Source Type: Journal    
DOI: None     Document Type: Review

References (116)

1. Katrak SM. The origin of HIV and AIDS: An enigma of evolution. Ann Indian Acad Neurol 2006; 9: 5-10.
2. Levy JA, Shimabukuro J, Hollander H, Mills J, Kaminsky L. Isolation of AIDS-associated retroviruses from cerebrospinal fl uid and brain of patients with neurological symptoms. Lancet 1985; 2: 586-8.
3. Lazarini F, Seilhean D, Rosenblum O, Suarez S, Conquy L, Uchihara T, et al. Human immunodeficiency virus type 1 DNA and RNA load in brains of demented and nondemented patients with acquired immunodefi ciency syndrome. J Neurovirol 1997; 3: 299-303.
4. Biniek R, Bartholome M, Schulz M, Lehmann HJ, Gesemann H, Scheiermann N, et al. Intrathecal production of HIV antibodies in suspected AIDS encephalopathy. J Neurol 1988; 235: 131-5.
5. Nath A, Sacktor N. Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system. Curr Opin Neurol 2006; 19: 358-61.
6. Satishchandra P, Nalini A, Gourie-Devi M, Khanna N, Santosh V, Ravi V, et al. Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96). Indian J Med Res 2000; 111: 14-23.
7. Buckner CM, Luers AJ, Calderon TM, Eugenin EA, Berman JW. Neuroimmunity and the blood-brain barrier: molecular regulation of leukocyte transmigration and viral entry into the nervous system with a focus on neuroAIDS. J Neuroimmune Pharmacol 2006; 1: 160-81.
8. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, et al. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 1986; 233: 1089-93.
9. Gorry PR, Ong C, Thorpe J, Bannwarth S, Thompson KA, Gatignol A, et al. Astrocyte infection by HIV-1: mechanisms of restricted virus replication and role in the pathogenesis of HIV-1-associated dementia. Curr HIV Res 2003; 1: 463-73.
10. Mattson MP, Haughey NJ, Nath A. Cell death in HIV dementia. Cell Death Differentiation 2005; 12 (Suppl 1): 893-904.
11. Boska MD, Mosley RL, Nawab M, Nelson JA, Zelivyanskaya M, Poluektova L, et al. Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring. Curr HIV Res 2004; 2: 61-78.
12. Epstein LG, Gendelman HE. Human immunodeficiency virus type-1 infection of the nervous system: pathogenetic mechanisms. Ann Neurol 1993; 33: 429-36.
13. Boron WF, Boulpaep EL. Medical physiology: a cellular and molecular approach. 1st ed. Philadelphia: W.B. Saunders; 2003. p. 94-420.
14. Aquaro S, Ronga L, Pollicita M, Antinori A, Ranazzi A, Perno CF. Human immunodeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage. J Neurovirol 2005; 11 (Suppl 3): 58-66.
15. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA1986; 83: 7089-93.
16. Sharer LR, Saito Y, Epstein LG, Blumberg BM. Detection of HIV-1 DNA in pediatric AIDS brain tissue by two-step ISPCR. Adv Neuroimmunol 1994; 4: 283-5.
17. Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E. Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex. Neurology 1999; 52: 100-4.
18. Gongvatana A, Woods SP, Taylor MJ, Vigil O, Grant I; HNRC Group. Semantic clustering inefficiency in HIV-associated dementia. J Neuropsyc Clin Neurosci 2007; 19: 36-42.
19. Riedel D, Ghate M, Nene M, Paranjape RS, Mehendale S, Bollinger R, et al. Screening for human immunodeficiency virus (HIV) dementia in an HIV clade C-infected population in India. J Neurovirol 2006; 12: 34-8.
20. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 2001; 193: 905-16.
21. Williams K, Hickey WF. Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 2002; 25: 537-62.
22. Peters PJ, Bhattacharya J, Hibbitts S, Dittmar MT, Simmons G, Bell J, et al. Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages. J Virol 2004; 78: 6915-26.
23. Raja F, Sherriff FE, Morris CS, Bridges LR, Esiri MM. Cerebral white matter damage in HIV infection demonstrated using ß-amyloid precursor protein immunoreactivity. Acta Neuropathol 1997; 93: 184-9.
24. Rothenaigner I, Kramer S, Ziegler M, Wolff H, Kleinschmidt A, Brack-Werner R. Long-term HIV-1 infection of neural progenitor populations. AIDS 2007; 21: 2271-81.
25. Lawrence DM, Durham LC, Schwartz L, Seth P, Maric D, Majo E. Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells. J Virol 2004; 78: 7319-28.
26. Rubin L, Staddon J. The cell biology of the blood brain barrier. Ann Rev NeuroSci 1999; 22: 11-27.
27. Bechmann I, Galea I, Perry VH. What is the blood brain barrier (not)? Trends Immunol 2007; 28: 5-11.
28. Persidsky Y, Zheng J, Miller D, Gendelman HE. Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. J Leukoc Biol 2000; 68: 413-22.
29. Sanders P, Mehta R. A murine model of HIV encephalitis: xenotransplantation of HIV-infected human neuroglia into SCID mouse brain. Neuropath Appl Neurobiol 1998; 24: 461-7.
30. Petito CK, Cash KS. Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 1992; 32: 658-66.
31. Argyris E, Acheampong E, Nunnari G, Muhammad M, Williams K, Pomerantz R. Human immunodeficiency virus type 1 enters primary human brain microvascular endothelial cells by a mechanism involving cell surface proteoglycans independent of lipid rafts. J Virol 2003; 77: 12140-51.
32. Conant K, McArthur JC, Griffin DE, Sjulson L, Wahl L, Irani D. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann Neurol 2001; 46: 391-8.
33. HIV dementia: why might some viruses cause more problems than others? [Database on the internet]. Theo Smart: aids map news. Available from http://www.aidsmap.com/en/news/ D045686F-8404-4B20-A217-B86D51279A01.asp, accessed on May 18, 2007.
34. András IE, Pu H, Deli MA, Nath A, Hennig B, Toborek M. HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. J Neurosci Res 2003; 74: 255-65.
35. Dietmar V. ICAM-2 and PECAM-1: 2 steps in leukocyte transmigration. Blood 2006; 107: 4579-80.
36. Muller WA, Weigl SA, Deng X, Phillips DM. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med 1993; 178: 449-60.
37. Wadia JS, Stan RV, Dowdy SF. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 2004; 10: 310-5.
38. Tornatore C, Chandra R, Berger JR, Major EO. HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 1994; 44: 481-7.
39. Liu Y, Liu H, Kim B, Gattone V, Li J, Nath A, et al. CD4-Independent infection of astrocytes by human immunodeficiency virus type 1: requirement for the human mannose receptor. J Virol 2004; 78: 4120-33.
40. Gorry PR, Howard JL, Churchill MJ, Anderson L, Cunningham A, Adrian D, et al. Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev. J Virol 1999; 73: 352-61.
41. Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, et al. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci USA 2006; 103: 15160-5.
42. Peters PJ, Sullivan WM, Duenas-Decamp MJ, Bhattacharya J, Ankghuambom C, Brown R, et al. Non-macrophagetropic human immunodeficiency virus type 1 R5, envelopes predominate in blood, lymph nodes, and semen: implications for transmission and pathogenesis. J Virol 2006; 80: 6324-32.
43. Fitting S, Booze RM, Hasselrot U, Mactutus CF. Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: a design-based stereological study. Hippocampus 2008; 18: 135-47.
44. Kingsman SM, Kingsman AJ. The regulation of human immunodeficiency virus type-1 gene expression. Eur J Biochem 1996; 240: 491-507.
45. Burdo TH, Gartner S, Mauger D, Wigdahl B. Region-specific distribution of human immunodeficiency virus type 1 long terminal repeats containing specific configurations of CCAAT/enhancer-binding protein site II in brains derived from demented and non demented patients. J Neurovirol 2004; 10(Suppl 1): 7-14.
46. Burdo TH, Nonnemacher M, Irish BP, Choi CH, Krebs FC, Gartner S, et al. High-affinity interaction between HIV-1 Vpr and specific sequences that span the C/EBP and adjacent NF-kappaB sites within the HIV-1 LTR correlate with HIV-1-associated dementia. DNA Cell Biol 2004; 23: 261-9.
47. Ross HL, Nonnemacher MR, Hogan TH, Quiterio SJ, Henderson A, McAllister JJ, et al. Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/ macrophage lineage. J Virol 2001; 75: 18-42.
48. McAllister JJ, Millhouse S, Krebs FC, Corboy J, Wigdahl B. Brain-derived HIV-1 isolates contain NF-kappaB-proximal Sp binding sites which fail to bind Sp factors and result in cell specific alterations in viral regulation. Neuroscience of HIV Infection. J Neurovirol 1998; 4: 359-66.
49. Marban C, Redel L, Suzanne S, Van LC, Lecestre D, Chasserot-Golaz S, et al. COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells. Nucleic Acids Res 2005; 33: 2318-31.
50. Jeeninga RE, Hoogenkamp M, Armand-Ugon M, de Baar M, Verhoef K, Berkhout B. Functional differences between the LTR transcriptional promoters of HIV-1 subtypes A through G. J Virol 2000; 74: 3740-51.
51. Moodley P, Smith AN, Madurai S, Tarin M, Cassol S. Phylogenetic variation of the Ltr and Nef genes in HIV infected Indians in KwaZulu Natal. Int Conf AIDS 2002 July 7-12; Durban, South Africa. Available from: http://gateway.nlm.nihgov/meetingabstracts/ ma?f=102249686.html.
52. Power C, McArthur JC, Johnson RT, Griffin DE, Glass JD, Perryman S, et al. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol 1994; 68: 4643-9.
53. Thomas E, Dunfee R, Stanton J, Bogdan D, Taylor J, Kunstaman K, et al. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion. Virology 2007; 360: 105-19.
54. Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 2000; 100: 587-97.
55. Bobardt MD, Salmon P, Wang L, Esko JD, Gabuzda D, Fiala M, et al. Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J Virol 2004; 78: 6567-84.
56. Okamoto S, Kang Y-J, Brechtel EW, Siviglia E, Russo R, et al. HIV/ gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest. Cell Stem Cell 2007; 1: 230-6.
57. Zhang K, Hawken M, Rana F, Welte FJ, Gartner S, Goldsmith MA, et al. Human immunodeficiency virus type 1 clade A and D neurotropism: Molecular evolution, recombination, and coreceptor use. Virology 2001; 283: 19-30.
58. Hudson L, Liu J, Nath A, Jones M, Raghavan R, Narayan O, et al. Detection of the human immunodeficiency virus regulatory protein Tat in CNS tissues. J Neurovirol 2000; 6: 145-55.
59. Sui Z, Sniderhan LF, Schifitto G, Phipps RP, Gelbard HA, Dewhurst S, et al. Functional synergy between CD40 ligand and HIV-1 Tat contributes to inflammation: implications in HIV type 1 dementia. J Immunol 2007; 178: 3226-36.
60. Chauhan A, Turchan J, Pocernich C, Bruce-Keller A, Roth S, Butterfield DA, et al. Intracellular human immunodeficiency virus tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport. J Biol Chem 2003; 278: 13512-9.
61. Eugenin EA, King JE, Nath A, Calderon TM, Zukin RS, Bennett V, et al. HIV-Tat induces formation of an LRP-PSD-95-NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci USA 2007; 104: 3438-43.
62. Amini S, Mameli G, Del Valle L, Skowronska A, Reiss K, Gelman BB. p73 interacts with human immunodeficiency virus type 1 tat in astrocytic cells and prevents its acetylation on lysine 28. Mol Cell Biol 2005; 25: 8126-38.
63. Ranga U, Shankarappa R, Siddappa BN, Ramakrishna L, Nagendran R, Mahalingam M, et al. Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. J Virol 2004; 78: 2586-90.
64. Sabatier J-M, Vives E, Marbouk K, Benjouad A, Rochat H, Duval A, et al. Evidence for neurotoxic activity of Tat from human immunodeficiency virus type-1. J Virol 1991; 65: 961-7.
65. Sabbah EN, Roques BP. Critical implication of the (70-96) domain of human immunodeficiency virus type 1 Vpr protein in apoptosis of primary rat cortical and striatal neurons. J Neurovirol 2005; 11: 489-502.
66. Le Rouzic E, Benichou S. The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology 2005; 2: 11.
67. Poon B, Chang MA, Chen IS. Vpr is required for efficient nef expression from unintegrated human immunodeficiency virus type 1 DNA. J Virol 2007; 81: 10515-23.
68. Acheampong EA, Parveen Z, Muthoga LW, Kalayeh M, Mukhtar M, Pomerantz RJ. Human immunodeficiency virus type 1 Nef potently induces apoptosis in primary human brain microvascular endothelial cells via the activation of caspases. Virology 2005; 79: 4257-69.
69. Swingler S, Brichacek B, Jacque J-M, Ulich C, Zhou J, Stevenson M. HIV-1 nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature 2003; 424: 213-9.
70. 2 AG-infected Ivorian (West Africa). AIDS Res Hum Retroviruses 2005; 21: 620-8.
71. Lavi E, Kolson DL, Ulrich AA, Fu L, GonzaÂlez-Scarano F. Chemokine receptors in the human brain and their relationship to HIV infection. J Neurovirol 1998; 4: 301-11.
72. Lehner T. The role of CCR5 chemokine ligands and antibodies to CCR5 coreceptors in preventing HIV infection. Trends Immunol 2002; 23: 347-51.
73. Griffin DE. Cytokines in the brain during viral infection: clues to HIV-associated dementia. J Clin Invest 1997; 100: 2948-51.
74. Kelder W, McArthur JC, Nance-Sproson T, McClernon D, Griffin DE. Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 1998; 44: 831-5.
75. Nebuloni M, Ottoni L, Bonetto S, Caldarelli R, Cinque P, Costanzi G, et al. Immunochemical evaluation of RANTES distribution in brains with HIV encephalitis. Neuroscience of HIV infection. J Neurovirol 1998; 4 (Suppl): 361-6.
76. Kaul M, Lipton SA. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci USA 1999; 96: 8212-6.
77. Schmidtmayerova H, Nottet HS, Nuovo G, Raabe T, Flanagan CR, Dubrovsky L, et al. Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. Proc Natl Acad Sci USA 1996; 93: 700-4.
78. Ransohoff RM, Tani M. Do chemokines mediate leukocyte recruitment in post-traumatic CNS inflammation? Trends Neurosci 1998; 21: 154-9.
79. Sasseville VG, Smith MM, Mackay CR, Pauley DR, Mansfield KG, Ringler DJ, et al. Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis. Am J Path 1996; 149: 1459-67.
80. Genis P, Jett M, Bernton EW, Boyle T, Gelbard HA, Dzenko K, et al. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 1992; 176: 1703-18.
81. Monteiro de Almeida, Letendre S, Zimmerman J, Kolakowski S, Lazzaretto D, McCutchan JA, et al. Relationship of CSF leukocytosis to compartmentalized changes in MCP-1/CCL2 in the CSF of HIV-infected patients undergoing interruption of antiretroviral therapy. J Neuroimmunol 2006; 179: 180-5.
82. Ragin AB, Wu Y, Storey P, Cohen BA, Edelman RR, Epstein LG. Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection. Neurology 2006; 66: 1255-60.
83. Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW. CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 2006; 26: 1098-106.
84. Copeland KF, Fransen S, Emtage P, Palmer K, McKay P, Gauldie J, et al; Conference on Retrovirus and Opportunistic Infections. The chemokines IP-10 and lymphotactin enhance HIV-1 long terminal repeat mediated gene expression in monocytic cells. Program Abstr Conf Retrovir Oppor Infect 1999 Jan 31-Feb4 6th Chicago Illinois 170 (abstract no. 547). Available from: http://gateway.nlm.nih.gov/ MeetingAbstracts/ma?F-102195315.html.
85. Luster AD, Greenberg SM, Leder P. The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. J Exp Med 1995; 182: 219-31.
86. Buch S, Sui Y, Potula R, Narayan O, Nath A, Kolson D; Conference on Retrovirus and Opportunistic Infections. Neuronal apoptosis is mediated by IP-10 over-expression in Simian human immunodeficiency virus encephalitis. Program Abstr Conf Retrovir Oppor Infect 2004 Feb 8-11 11th San Francisco California: abstract no. 473. Available from: http://gateway.nlm.nih.gov/MeetingAbstracts/ ma?F-102271436.html.
87. Johnston JB, Jiang Y, van Marle G, Mayne MB, Ni W, Holden, et al. Lentivirus infection in the brain induces matrix metalloproteinase expression: Role of envelope diversity. J Virol 2000; 74: 7211-20.
88. Rumbaugh J, Turchan-Cholewo J, Galey D, St. Hillaire C, Anderson C, Conant K, et al. Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism. FASEB J 2006; 20: 1736-8.
89. Misseé D, Esteve PO, Renneboog B, Vidal M, Cerutti M, St Pierre Y, et al. HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway. Blood 2001; 98: 541-7.
90. Merrill JE, Koyanagi Y, Zack J, Thomas L, Martin F, Chen IS. Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. J Virol 1992; 66: 2217-25.
91. Ghorpade A, Borgmann K, Schellpepper C, Holter S, Persidsky R, Zheng J, et al; Conference on Retroviruses and Opportunistic Infections. IL-1 beta-activated astrocytes express fas ligand: novel pathways to neuronal injury in HIV-1-associated dementia. Conf Retrovir Oppor Infect 2002 Washington Feb 24-28; 9: abstract no. 738-W. Available from: http://gateway.nlm.nih.gov/MeetingAbstracts /ma?f=102264037.html.
92. Fiala M, Looney DJ, Stins M, Way DD, Zhang L, Gan X, et al. TNF-alpha opens a paracellular route for HIV-1 invasion across the blood-brain barrier. Mol Med 1997; 3: 553-64.
93. Miura Y, Koyanagi Y, Mizusawa H. TNF-related apoptosis-inducing ligand (TRAIL) induces neuronal apoptosis in HIV-encephalopathy. J Med Dent Sci 2003; 50: 17-25.
94. Yeung M, Pulliam L, Lau A. The HIV membrane gp120 protein is toxic to human brain cell cultures through the induction of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). American Pediatric Society 104th annual meeting and Society for Pediatric Research 63rd annual meeting; 1994 May 2-5; Seattle. Pediatr AIDS HIV Infect 1995; 5: 317-24.
95. Gardner J, Ghorpade A. Tissue inhibitor of metalloproteinase (TIMP)-1: The TIMPed balance of matrix metalloproteinases in the central nervous system. J Neurosci Res 2003; 74: 801-6.
96. Si Q, Cosenza M, Zhao ML, Goldstein H, Lee SC. GM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia. Glia 2002; 39: 174-83.
97. Rumbaugh R, Jeffery A, Nath A. Development in HIV neuropathogenesis. Curr Pharmaceut Des 2006; 12: 1023-44.
98. 2+ influx, synergism with platelet-activating factor and significance for chemotaxis. J Biol Chem 1994; 269: 4746-53.
99. Vanzani MC, Iacono RF, Caccuri RL, Troncoso AR, Berria MI. Regional differences in astrocyte activation in HIV-associated dementia. Medicina (B Aires) 2006; 66: 108-12.
100. Dimitrov DS, Broder CC, Berger EA, Blumenthal R. Calcium ions are required for cell fusion mediated by the CD4-human immunodeficiency virus type 1 envelope glycoprotein interaction. J Virol 1993; 67: 1647-52.
101. Haughey NJ, Mattson MP. Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. J Acquir Immune Defic Syndr 2002; 31 (Suppl 2): S55-61.
102. Ferrarese C, Aliprandi A, Tremolizzo L, Stanzani L, De Micheli A, Dolara A. Increased glutamate in CSF and plasma of patients with HIV dementia. Neurology 2001; 57: 671-5.
103. Chrétien F, Vallat-Decouvelaere AV, Bossuet C, Rimanio AC, Le Grand R, Le Pavec G, et al. Expression of excitatory amino acid transporter-2 (EAAT-2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251-infected macaques. Neuropathol Appl Neurobiol 2002; 28: 410-7.
104. Kaul M, Lipton SA. The NMDA receptor - its role in neuronal apoptosis and HIV-associated dementia. NeuroAids 2000; 3: 6-12.
105. Haughey NJ, Nath A, Mattson MP, Slevin JT, Geiger JD. HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. J Neurochem 2001; 78: 457-67.
106. Prevalence of HIV-related dementia second only to Alzheimer's, stroke [database on the internet] Caroline Cassels: MedScape Medical News. Available from http://www.medscape.com/viewarticle/551884, accessed on February 8, 2007.
107. HIV and the brain: [database on the internet] aids map: treatment and care. Available from http://www.aidsmap.com/cms1032592.asp.
108. Kruman II, Nath A, Mattson MP. HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol 1998; 154: 276-88.
109. Sweetnam PM, Saab OH, Wroblewski JT, Price CH, Karbon W, Ferkany JW. The envelope glycoprotein of HIV-1 alters NMDA receptor function. Eur J Neurosci 1993; 5: 276-83.
110. Cheng X, Mukhtar M, Acheampong EA, Srinivasan A, Rafi M, Pomerantz R, et al. HIV-1 Vpr potently induces programmed cell death in the CNS in vivo. DNA Cell Biol 2007; 26: 116-31.
111. Matsubara M, Jing T, Kawamura K, Shimojo N, Titani K, Hashimoto K, et al. Myristoyl moiety of HIV Nef is involved in regulation of the interaction with calmodulin in vivo. Protein Sci 2005; 14: 494-503.
112. Pomerantz R, Xu Y, Sullivan J, Kulkosky J; Conference on Retroviruses and Opportunistic Infections. HIV-1-mediated apoptosis of neurons: The proximal mechanisms of HIV-1-induced encephalopathy Program Abstr. Conference on Retroviruses and Opportunistic Infections 11th 2004: San Francisco, California. Feb 8-11; 11: abstract no. 32. Available from: http://gateway.nlm.nih.gov/MeetingAbstracts /ma?f=102270899.html.
113. Kaul M, Garden GA, Lipton SA. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 2001; 410: 988-94.
114. Gu Z, Kaul M, Yan B, Kridel S, Cui J, Strongin A, et al. S-nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death. Science 2002; 297: 1186-90.
115. Yeh MW, Kaul M, Zheng J, Nottet HS, Thylin M, Gendelman HE, et al. Cytokine-stimulated, but not HIV-infected, human monocyte-derived macrophages produce neurotoxic levels of L-cysteine. J Immunol 2000; 164: 4265-70.
116. Huang Y, Erdmann N, Peng H, Herek S, Davis JS, Luo X, et al. TRAIL-mediated apoptosis in HIV-1-infected macrophages is dependent on the inhibition of Akt-1 phosphorylation. J Immunol 2006; 177: 2304-13.