Journal of Neuroimmune Pharmacology

, Volume 5, Issue 1, pp 44–62 | Cite as

Gene Expression Profiles of HIV-1-Infected Glia and Brain: Toward Better Understanding of the Role of Astrocytes in HIV-1-Associated Neurocognitive Disorders

  • Alejandra Borjabad
  • Andrew I. Brooks
  • David J. Volsky
Invited Review

Abstract

Astrocytes are the major cellular component of the central nervous system (CNS), and they play multiple roles in brain development, normal brain function, and CNS responses to pathogens and injury. The functional versatility of astrocytes is linked to their ability to respond to a wide array of biological stimuli through finely orchestrated changes in cellular gene expression. Dysregulation of gene expression programs, generally by chronic exposure to pathogenic stimuli, may lead to dysfunction of astrocytes and contribute to neuropathogenesis. Here, we review studies that employ functional genomics to characterize the effects of HIV-1 and viral pathogenic proteins on cellular gene expression in astrocytes in vitro. We also present the first microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. In spite of different experimental conditions and microarray platforms used, comparison of the astrocyte array data sets reveals several common gene-regulatory changes that may underlie responses of these cells to HIV-1 and its proteins. We also compared the transcriptional profiles of astrocytes with those obtained in analyses of brain tissues of patients with HIV-1 dementia and macaques infected with simian immunodeficiency virus (SIV). Notably, many of the gene characteristics of responses to HIV-1 in cultured astrocytes were also altered in HIV-1 or SIV-infected brains. Functional genomics, in conjunction with other approaches, may help clarify the role of astrocytes in HIV-1 neuropathogenesis.

Keywords

astrocytes microarrays gene expression profiling HIV-1 HAD brain neurobiology neurodegeneration innate immunity 

References

  1. Alirezaei M, Watry DD, Flynn CF, Kiosses WB, Masliah E, Williams BR, Kaul M, Lipton SA, Fox HS (2007) Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons. J Neurosci 27:11047–11055PubMedCrossRefGoogle Scholar
  2. An SF, Groves M, Giometto B, Beckett AAJ, Scaravilli F (1999) Detection and localisation of HIV-1 DNA and RNA in fixed adult AIDS brain by polymerase chain reaction/in situ hybridisation technique. Acta Neuropathol 98:481–487PubMedCrossRefGoogle Scholar
  3. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64:529–536PubMedGoogle Scholar
  4. Antinori A et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRefGoogle Scholar
  5. Arancibio-Cárcamo IL, Kittler JT (2009) Regulation of GABA(A) receptor membrane trafficking and synaptic localization. Pharmacol Ther 123:17–31CrossRefGoogle Scholar
  6. Aravalli RN, Hu S, Rowen TN, Gekker G, Lokensgard JR (2006) Differential apoptotic signaling in primary glial cells infected with herpes simplex virus 1. J Neurovirology 12:501–510CrossRefGoogle Scholar
  7. Bachoo RM, Kim RS, Ligon KL, Maher EA, Brennan C, Billings N, Chan S, Li C, Rowitch DH, Wong WH, DePinho RA (2004) Molecular diversity of astrocytes with implications for neurological disorders. Proc Natl Acad Sci USA 101:8384–8389PubMedCrossRefGoogle Scholar
  8. Benos DJ, Hahn BH, Bubien JK, Ghosh SK, Mashburn NA, Chaikin MA, Shaw GM, Benveniste EN (1994) Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transport in astrocytes: implications for AIDS dementia complex. Proc Natl Acad Sci USA 91:494–498PubMedCrossRefGoogle Scholar
  9. Benveniste EN, Shrikant P, Patton HK, Benos DJ (1998) Neuroimmunologic mechanisms for disease in AIDS: The role of the astrocyte. In: Gendelman HE, Lipton AS, Epstein L, Swindells S (eds) The neurology of AIDS. Chapman & Hall, New York, pp 130–146Google Scholar
  10. Bezzi P, Volterra A (2001) A neuron-glia signalling network in the active brain. Curr Opin Neurobiol 11:387–394PubMedCrossRefGoogle Scholar
  11. Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFa: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710PubMedCrossRefGoogle Scholar
  12. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW (2004) Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 101:2173–2178PubMedCrossRefGoogle Scholar
  13. Boukerche H, Su ZZ, Kang DC, Fisher PB (2007) Cloning differentially expressed genes using rapid subtraction hybridization (RaSH). Methods Mol Biol 383:15–29PubMedCrossRefGoogle Scholar
  14. Brack-Werner R (1999) Astrocytes: HIV cellular reservoirs and important participants in neuropathogenesis. AIDS 13:1–22PubMedCrossRefGoogle Scholar
  15. Brazma A et al (2001) Minimum information about a microarray experiment (MIAME)—toward standards for microarray data. Nat Genet 29:365–371PubMedCrossRefGoogle Scholar
  16. Buch S, Sui Y, Dhillon N, Potula R, Zien C, Pinson D, Li S, Dhillon S, Nicolay B, Sidelnik A, Li C, Villinger T, Bisarriya K, Narayan O (2004) Investigations on four host response factors whose expression is enhanced in X4 SHIV encephalitis. J Neuroimmunol 157:71–80PubMedCrossRefGoogle Scholar
  17. Budka H (1991) Neuropathology of human immunodeficiency virus infection. Brain Pathol 1:163–175PubMedCrossRefGoogle Scholar
  18. Budka H (2005) The neuropathology of HIV-associated brain disease. In: Gendelman HE, Grant I, Everall IP, Lipton SA, Swindells S (eds) The Neurology of AIDS, 2nd edn. Oxford University Press, New York, pp 375–391Google Scholar
  19. Cai Y, Liu Y, Yu D, Zhang X (2003) Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection. Virology 316:104–115PubMedCrossRefGoogle Scholar
  20. Canki M, Thai JNF, Chao W, Ghorpade A, Potash MJ, Volsky DJ (2001) Highly productive infection with pseudotyped human immunodeficiency virus type 1 (HIV-1) indicates no intracellular restrictions to HIV-1 Replication in primary human astrocytes. J Virol 75:7925–7933PubMedCrossRefGoogle Scholar
  21. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36:827–835PubMedCrossRefGoogle Scholar
  22. Chen B, Bixby JL (2005) A novel substrate of receptor tyrosine phosphatase PTPRO is required for nerve growth factor-induced process outgrowth. J Neurosci 25:880–888PubMedCrossRefGoogle Scholar
  23. Chen JJ, Hsueh HM, Delongchamp RR, Lin CJ, Tsai CA (2007) Reproducibility of microarray data: a further analysis of microarray quality control (MAQC) data. BMC Bioinformatics 8:412PubMedCrossRefGoogle Scholar
  24. Chung C, Tallerico T, Seeman P (2003) Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene. Synapse 50:29–34PubMedCrossRefGoogle Scholar
  25. Churchill GA (2002) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32:490–495PubMedCrossRefGoogle Scholar
  26. Cobb JP et al (2005) Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci USA 102:4801–4806PubMedCrossRefGoogle Scholar
  27. Conant K, Major EO (1998) Astrocytes as mediators of CNS injury in AIDS. In: Gendelman HE, Lipton AS, Epstein L, Swindells S (eds) The neurology of AIDS. Chapman & Hall, New York, pp 147–155Google Scholar
  28. Conant K, Garzino-Demo A, Nath A, McArthur JC, Halliday W, Power C, Gallo RC, Major EO (1998) Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS. Proc Natl Acad Sci USA 95:3117–3121PubMedCrossRefGoogle Scholar
  29. Cosenza-Nashat MA, Si Q, Zhao ML, Lee SC (2006) Modulation of astrocyte proliferation by HIV-1: differential effects in productively infected, uninfected, and Nef-expressing cells. J Neuroimmunol 178:87–99PubMedCrossRefGoogle Scholar
  30. Cota M, Kleinschmidt A, Ceccherini-Silberstein F, Aloisi F, Mengozzi M, Mantovani A, Brack-Werner R, Poli G (2000) Upregulated expression of interleukin-8, RANTES, and chemokine receptors in human astrocytic cells infected with HIV-1. J Neurovirology 6:75–83CrossRefGoogle Scholar
  31. Cui X, Churchill GA (2003) Statistical tests for differential expression in cDNA microarray experiments. Genome Biol 4:210PubMedCrossRefGoogle Scholar
  32. D’Agata V, Cavallaro S (2004) Genomic portraits of the nervous system in health and disease. Neurochem Res 29:1201–1212PubMedCrossRefGoogle Scholar
  33. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105PubMedCrossRefGoogle Scholar
  34. Davies DL, Niesman IR, Boop FA, Phelan KD (2000) Heterogeneity of astroglia cultured from adult human temporal lobe. Int J Dev Neurosci 18:151–160PubMedCrossRefGoogle Scholar
  35. De Muth JE (2009) Overview of biostatistics used in clinical research. Am J Health Syst Pharm 66:70–81PubMedCrossRefGoogle Scholar
  36. Ding L, Hegde AN (2008) Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients. Biol Psychiatry 65:541–545PubMedCrossRefGoogle Scholar
  37. Doniger SW, Salomonis N, Dahlquist KD, Vranizan K, Lawlor SC, Conklin BR (2003) MAPPFinder: using gene ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol 4:R7PubMedCrossRefGoogle Scholar
  38. Dou H, Morehead J, Bradley J, Gorantla S, Ellison B, Kingsley J, Smith LM, Chao W, Bentsman G, Volsky DJ, Gendelman HE (2006) Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. Glia 54:81–93PubMedCrossRefGoogle Scholar
  39. Dufva M, Flodin J, Nerstedt A, Ruetschi U, Rymo L (2002) Epstein–Barr virus nuclear antigen 5 inhibits pre-mRNA cleavage and polyadenylation. Nucleic Acids Res 30:2131–2143PubMedCrossRefGoogle Scholar
  40. El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF (2005) Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia 50:91–106PubMedCrossRefGoogle Scholar
  41. El-Hage N, Bruce-Keller AJ, Yakovleva T, Bazov I, Bakalkin G, Knapp PE, Hauser KF (2008) Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through convergent effects on [Ca2+]i, NF-kB trafficking and transcription. PLoS ONE 3:e4093PubMedCrossRefGoogle Scholar
  42. 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
  43. Everall I, Luthert P, Lantos P (1993) A review of neuronal damage in human immunodeficiency virus infection: its assessment, possible mechanism and relationship to dementia. J Neuropathol Exp Neurol 52:561–566PubMedCrossRefGoogle Scholar
  44. Everall I, Salaria S, Roberts E, Corbeil J, Sasik R, Fox H, Grant I, Masliah E (2005) Methamphetamine stimulates interferon inducible genes in HIV infected brain. J Neuroimmunol 170:158–171PubMedCrossRefGoogle Scholar
  45. Everall IP, Salaria S, Atkinson JH, Young C, Corbeil J, Grant I, Masliah E (2006) Diminished somatostatin gene expression in individuals with HIV and major depressive disorder. Neurology 67:1867–1869PubMedCrossRefGoogle Scholar
  46. Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138–145PubMedCrossRefGoogle Scholar
  47. Fine SM, Angel RA, Perry SW, Epstein LG, Rothstein JD, Dewhurst S, Gelbard HA (1996) Tumor necrosis factor a inhibits glutamate uptake by primary human astrocytes. J Biol Chem 271:15303–15306PubMedCrossRefGoogle Scholar
  48. Galey D, Becker K, Haughey N, Kalehua A, Taub D, Woodward J, Mattson M, Nath A (2003) Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes. J Neurovirology 9:358–371Google Scholar
  49. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219PubMedCrossRefGoogle Scholar
  50. Gebicke-Haerter PJ (2005) Microarrays and expression profiling in microglia research and in inflammatory brain disorders. J Neurosci Res 81:327–341PubMedCrossRefGoogle Scholar
  51. Gegelashvili M, Rodriguez-Kern A, Sung L, Shimamoto K, Gegelashvili G (2007) Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes. Neurochem Int 50:916–920PubMedCrossRefGoogle Scholar
  52. Gelman BB, Soukup VM, Schuenke KW, Keherly MJ, Holzer C 3rd, Richey FJ, Lahart CJ (2004) Acquired neuronal channelopathies in HIV-associated dementia. J Neuroimmunol 157:111–119PubMedCrossRefGoogle Scholar
  53. Genis P, Jett M, Bernton EW, Boyle T, Gelbard HA, Dzenko K, Keane RW, Resnick L, Mizrachi Y, Volsky DJ, Epstein LG, Gendelman HE (1992) Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage–astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 176:1703–1718PubMedCrossRefGoogle Scholar
  54. Glabinski AR, Ransohoff RM (1999) Chemokines and chemokine receptors in CNS pathology. J Neurovirology 5:3–12CrossRefGoogle Scholar
  55. Glanzer JG, Haydon PG, Eberwine JH (2004) Expression profile analysis of neurodegenerative disease: advances in specificity and resolution. Neurochem Res 29:1161–1168PubMedCrossRefGoogle Scholar
  56. Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–537PubMedCrossRefGoogle Scholar
  57. González-Scarano F, Martín-García J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81PubMedCrossRefGoogle Scholar
  58. Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2003) HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication. J Biosci 28:323–335PubMedCrossRefGoogle Scholar
  59. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA (2001) Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98:4746–4751PubMedCrossRefGoogle Scholar
  60. Hardiman G (2004) Microarray platforms—comparisons and contrasts. Pharmacogenomics 5:487–502PubMedCrossRefGoogle Scholar
  61. Hesselgesser J, Horuk R (1999) Chemokine and chemokine receptor expression in the central nervous system. J Neurovirology 5:13–26CrossRefGoogle Scholar
  62. Hoheisel JD (2006) Microarray technology: beyond transcript profiling and genotype analysis. Nat Rev Genet 7:200–210PubMedCrossRefGoogle Scholar
  63. Holden CP, Haughey NJ, Nath A, Geiger JD (1999) Role of Na+/H+ exchangers, excitatory amino acid receptors and voltage-operated Ca2+ channels in human immunodeficiency virus type 1 gp120-mediated increases in intracellular Ca2+ in human neurons and astrocytes. Neuroscience 91:1369–1378PubMedCrossRefGoogle Scholar
  64. Hosack DA, Dennis G Jr, Sherman BT, Lane HC, Lempicki RA (2003) Identifying biological themes within lists of genes with EASE. Genome Biol 4:R70PubMedCrossRefGoogle Scholar
  65. Irier HA, Shaw R, Lau A, Feng Y, Dingledine R (2009) Translational regulation of GluR2 mRNAs in rat hippocampus by alternative 3′ untranslated regions. J Neurochem 109:584–594PubMedCrossRefGoogle Scholar
  66. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31:e15PubMedCrossRefGoogle Scholar
  67. Jafari P, Azuaje F (2006) An assessment of recently published gene expression data analyses: reporting experimental design and statistical factors. BMC Med Inform Decis Mak 6:27PubMedCrossRefGoogle Scholar
  68. Jarvinen AK, Hautaniemi S, Edgren H, Auvinen P, Saarela J, Kallioniemi OP, Monni O (2004) Are data from different gene expression microarray platforms comparable? Genomics 83:1164–1168PubMedCrossRefGoogle Scholar
  69. Kang DC, Su ZZ, Sarkar D, Emdad L, Volsky DJ, Fisher PB (2005) Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene 353:8–15PubMedCrossRefGoogle Scholar
  70. Kapetanovic IM, Rosenfeld S, Izmirlian G (2004) Overview of commonly used bioinformatics methods and their applications. Ann N Y Acad Sci 1020:10–21PubMedCrossRefGoogle Scholar
  71. Kerr G, Ruskin HJ, Crane M, Doolan P (2008) Techniques for clustering gene expression data. Comput Biol Med 38:283–293PubMedCrossRefGoogle Scholar
  72. Khan J, Wei JS, Ringnér M, Saal LH, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu CR, Peterson C, Meltzer PS (2001) Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat Med 7:673–679PubMedCrossRefGoogle Scholar
  73. Kim SY, Volsky DJ (2005) PAGE: parametric analysis of gene set enrichment. BMC Bioinformatics 6:144PubMedCrossRefGoogle Scholar
  74. Kim SY, Chao W, Choi SY, Volsky DJ (2003) Cloning and characterization of the 3′-untranslated region of the human excitatory amino acid transporter 2 transcript. J Neurochem 86:1458–1467PubMedCrossRefGoogle Scholar
  75. Kim S-Y, Li J, Bentsman G, Brooks AI, Volsky DJ (2004) Microarray analysis of changes in cellular gene expression induced by productive infection of primary human astrocytes: implications for HAD. J Neuroimmunol 157:17–26PubMedCrossRefGoogle Scholar
  76. Kolson DL, Pomerantz RJ (1996) AIDS dementia and HIV-1-induced neurotoxicity: possible pathogenic associations and mechanisms. J Biomed Sci 3:389–414PubMedCrossRefGoogle Scholar
  77. Korn EL, Habermann JK, Upender MB, Ried T, McShane LM (2004) Objective method of comparing DNA microarray image analysis systems. Biotechniques 36:960–967PubMedGoogle Scholar
  78. Kramer-Hämmerle S, Hahn A, Brack-Werner R, Werner T (2005) Elucidating effects of long-term expression of HIV-1 Nef on astrocytes by microarray, promoter, and literature analyses. Gene 358:31–38PubMedCrossRefGoogle Scholar
  79. Krum JM, Mani N, Rosenstein JM (2008) Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury. Exp Neurol 212:108–117PubMedCrossRefGoogle Scholar
  80. Kutsch O, Oh J-W, Nath A, Benveniste EN (2000) Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 Tat in astrocytes. J Virology 74:9214–9221PubMedCrossRefGoogle Scholar
  81. Lavi E, Kolson LD, Ulrich MA, Fu L, González-Scarano F (1998) Chemokine receptors in the human brain and their relationship to HIV infection. J Neurovirology 4:301–311CrossRefGoogle Scholar
  82. Li J, Bentsman G, Potash MJ, Volsky DJ (2007) Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection. BMC Neurosci 8:31PubMedCrossRefGoogle Scholar
  83. Lipton S, Gendelman HE (1995) Dementia associated with the acquired immunodeficiency syndrome. New Engl J Med 233:934–940Google Scholar
  84. Liu X, Jana M, Dasgupta S, Koka S, He J, Wood C, Pahan K (2002) Human immunodeficiency virus type 1 (HIV-1) Tat induces nitric-oxide synthase in human astroglia. J Biol Chem 277:39312–39319PubMedCrossRefGoogle Scholar
  85. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8:500–508PubMedCrossRefGoogle Scholar
  86. Lukiw WJ (2004) Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling. Neurochem Res 29:1287–1297PubMedCrossRefGoogle Scholar
  87. MacDonald JL, Roskams AJ (2009) Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation. Prog Neurobiol 88:170–183PubMedCrossRefGoogle Scholar
  88. Maestre C, Delgado-Esteban M, Gomez-Sanchez JC, Bolaños JP, Almeida A (2008) Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity. EMBO J 27:2736–2745PubMedCrossRefGoogle Scholar
  89. Maragakis NJ, Dykes-Hoberg M, Rothstein JD (2004) Altered expression of the glutamate transporter EAAT2b in neurological disease. Ann Neurol 55:469–477PubMedCrossRefGoogle Scholar
  90. Martin KJ, Graner E, Li Y, Price LM, Kritzman BM, Fournier MV, Rhei E, Pardee AB (2001) High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood. Proc Natl Acad Sci USA 98:2646–2651PubMedCrossRefGoogle Scholar
  91. Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA (1992) Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 51:585–593PubMedCrossRefGoogle Scholar
  92. Masliah E, Roberts ES, Langford D, Everall I, Crews L, Adame A, Rockenstein E, Fox HS (2004) Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. J Neuroimmunol 157:163–175PubMedCrossRefGoogle Scholar
  93. McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157:3–10PubMedCrossRefGoogle Scholar
  94. McManus CM, Weidenheim K, Woodman SE, Nunez J, Hesselgesser J, Nath A, Berman JW (2000) Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation. Am J Pathol 156:1441–1453PubMedGoogle Scholar
  95. McOmish CE, Burrows EL, Howard M, Hannan AJ (2008) PLC-beta1 knockout mice as a model of disrupted cortical development and plasticity: behavioral endophenotypes and dysregulation of RGS4 gene expression. Hippocampus 18:824–834PubMedCrossRefGoogle Scholar
  96. Meeuwsen S, Persoon-Deen C, Bsibsi M, Ravid R, van Noort JM (2003) Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli. Glia 43(3):243–253CrossRefGoogle Scholar
  97. Mense SM, Sengupta A, Zhou M, Lan C, Bentsman G, Volsky DJ, Zhang L (2006) Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in primary human astrocytes. Physiol Genomics 25:435–449PubMedCrossRefGoogle Scholar
  98. Nakagawa T, Schwartz JP (2004) Gene expression patterns in in vivo normal adult astrocytes compared with cultured neonatal and normal adult astrocytes. Neurochem Int 45:203–242PubMedCrossRefGoogle Scholar
  99. Nam D, Kim SY (2008) Gene-set approach for expression pattern analysis. Brief Bioinform 9:189–197PubMedCrossRefGoogle Scholar
  100. Nath A, Hartloper V, Furer M, Fowke KR (1995) Infection of human fetal astrocytes with HIV-1: viral tropism and the role of cell to cell contact in viral transmission. J Neuropathol Exp Neurol 54:320–330PubMedCrossRefGoogle Scholar
  101. Navia BA, Price RW (1998) Clinical and biologic features of the AIDS dementia complex. In: Gendelman HE, Lipton SA, Epstein L, Swindells S (eds) The neurology of AIDS. Chapman & Hall, New York, pp 229–240Google Scholar
  102. Nuovo GJ, Alfieri ML (1996) AIDS dementia is associated with massive, activated HIV-1 infection and concomitant expression of several cytokines. Mol Med 2:358–366PubMedCrossRefGoogle Scholar
  103. Nuovo GJ, Gallery F, MacConnell P, Braun A (1994) In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acid and tumor necrosis-alpha RNA in the central nervous system. Am J Pathol 144:659–666PubMedGoogle Scholar
  104. Park JS, Seo J, Kim YO, Lee HS, Jo I (2009) Coordinated regulation of angiopoietin-1 and vascular endothelial growth factor by arsenite in human brain microvascular pericytes: implications of arsenite-induced vascular dysfunction. Toxicol (in press)Google Scholar
  105. Parmigiani G, Garrett-Mayer ES, Anbazhagan R, Gabrielson E (2004) A cross-study comparison of gene expression studies for the molecular classification of lung cancer. Clin Cancer Res 10:2922–2927PubMedCrossRefGoogle Scholar
  106. Pavlidis P, Qin J, Arango V, Mann JJ, Sibille E (2004) Using the gene ontology for microarray data mining: a comparison of methods and application to age effects in human prefrontal cortex. Neurochem Res 29:1213–1222PubMedCrossRefGoogle Scholar
  107. Radhakrishnan S, Otte J, Enam S, Del Valle L, Khalili K, Gordon J (2003) JC virus-induced changes in cellular gene expression in primary human astrocytes. J Virol 77:10638–10644PubMedCrossRefGoogle Scholar
  108. Ramaswamy S, Ross KN, Lander ES, Golub TR (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33:49–54PubMedCrossRefGoogle Scholar
  109. Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R, Haapasolo H, Krohn K (1995) Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9:1001–1008PubMedCrossRefGoogle Scholar
  110. Rivieccio MA, John GR, Song X, Suh HS, Zhao Y, Lee SC, Brosnan CF (2005) The cytokine IL-1beta activates IFN response factor 3 in human fetal astrocytes in culture. J Immunol 174:3719–3726PubMedGoogle Scholar
  111. Rivieccio MA, Suh HS, Zhao Y, Zhao ML, Chin KC, Lee SC, Brosnan CF (2006) TLR3 ligation activates an antiviral response in human fetal astrocytes: a role for viperin/cig5. J Immunol 177:4735–4741PubMedGoogle Scholar
  112. Roberts ES, Zandonatti MA, Watry DD, Madden LJ, Henriksen SJ, Taffe MA, Fox HS (2003) Induction of pathogenic sets of genes in macrophages and neurons in NeuroAIDS. Am J Pathol 162:2041–2057PubMedGoogle Scholar
  113. Roberts ES, Burudi EME, Flynn C, Madden LJ, Roinick KL, Watry DD, Zandonatti MA, Taffe MA, Fox HS (2004) Acute SIV infection of the brain leads to upregulation of IL6 and interferon-regulated genes: expression patterns throughout disease progression and impact on neuroAIDS. J Neuroimmunol 157:81–92PubMedCrossRefGoogle Scholar
  114. Ronaldson PT, Bendayan R (2006) HIV-1 viral envelope glycoprotein gp120 triggers an inflammatory response in cultured rat astrocytes and regulates the functional expression of P-glycoprotein. Mol Pharmacol 70:1087–1098PubMedCrossRefGoogle Scholar
  115. Rubio N, Sanz-Rodriguez F (2007) Induction of the CXCL1 (KC) chemokine in mouse astrocytes by infection with the murine encephalomyelitis virus of Theiler. Virology 358:98–108PubMedCrossRefGoogle Scholar
  116. Runne H, Régulier E, Kuhn A, Zala D, Gokce O, Perrin V, Sick B, Aebischer P, Déglon N, Luthi-Carter R (2008) Dysregulation of gene expression in primary neuron models of Huntington’s disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. J Neurosci 28:9723–9731PubMedCrossRefGoogle Scholar
  117. Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44:474–481PubMedGoogle Scholar
  118. Salaria S, Badkoobehi H, Rockenstein E, Crews L, Chana G, Masliah E, Everall IP (2007) Toll-like receptor pathway gene expression is associated with human immunodeficiency virus-associated neurodegeneration. J Neurovirol 13:496–503PubMedCrossRefGoogle Scholar
  119. Scharpf R, Garrett ES, Hu J, Parmigiani G (2003) Statistical modeling and visualization of molecular profiles in cancer. Biotechniques Suppl.:22–29Google Scholar
  120. Schubert D (1984) Developmental biology of cultured nerve, muscle, and glia. Wiley, New YorkGoogle Scholar
  121. Sengupta A, Mense SM, Lan C, Zhou M, Mauro RE, Kellerman L, Bentsman G, Volsky DJ, Louis ED, Graziano JH, Zhang L (2007) Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicol 28:478–489CrossRefGoogle Scholar
  122. Seth P, Koul N (2008) Astrocyte, the star avatar: redefined. J Biosci 33:405–421PubMedCrossRefGoogle Scholar
  123. Shapshak P, Duncan R, Torres-Muñoz JE, Duran EM, Minagar A, Petito CK (2004) Analytic approaches to differential gene expression in AIDS versus control brains. Front Biosci 9:2935–2946PubMedCrossRefGoogle Scholar
  124. Sharer LR, Epstein LG, Cho ES, Joshi VV, Meyenhofer MF, Rankin LF, Petito CK (1986) Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum Pathol 17:271–284PubMedCrossRefGoogle Scholar
  125. Silver DJ, Steindler DA (2009) Common astrocytic programs during brain development, injury and cancer. Trends Neurosci 32:303–311PubMedCrossRefGoogle Scholar
  126. Skoff RP, Knapp PE (1995) The origins and lineages of macroglial cells. In: Kettenmann H, Ransom BR (eds) Neuroglia. Oxford University Press, New York, pp 135–148Google Scholar
  127. Stephens EB, Jackson M, Cui L, Pacyniak E, Choudhuri R, Liverman CS, Salomon DS, Berman NE (2006) Early dysregulation of cripto-1 and immunomodulatory genes in the cerebral cortex in a macaque model of neuroAIDS. Neurosci Lett 410(2):94–99PubMedCrossRefGoogle Scholar
  128. Streit WJ (1995) Microglial cells. In: Kettenmann H, Ransom BR (eds) Neuroglia. Oxford University Press, New York, pp 85–96Google Scholar
  129. Z-z Su, D-c K, Chen Y, Pekarskaya O, Chao W, Volsky DJ, Fisher PB (2002) Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene 21:3592–3602CrossRefGoogle Scholar
  130. Su Z-Z, D-c K, Chen Y, Pekarskaya O, Chao W, Volsky DJ, Fisher PB (2003) Identification of gene products suppressed by human immunodeficiency virus type 1 infection or gp120 exposure of primary human astrocytes by rapid subtraction hybridization. J Neurovirology 9:372–389Google Scholar
  131. Sui Y, Potula R, Pinson D, Adany I, Li Z, Day J, Buch E, Segebrecht J, Villinger F, Liu Z, Huang M, Narayan O, Buch S (2003) Microarray analysis of cytokine and chemokine genes in the brains of macaques with SHIV-encephalitis. J Med Primatol 32:229–239PubMedCrossRefGoogle Scholar
  132. Sui Z, Fan S, Sniderhan L, Reisinger E, Litzburg A, Schifitto G, Gelbard HA, Dewhurst S, Maggirwar SB (2006) Inhibition of mixed lineage kinase 3 prevents HIV-1 Tat-mediated neurotoxicity and monocyte activation. J Immunol 177:702–711PubMedGoogle Scholar
  133. Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD (1996) Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol 39:705–711PubMedCrossRefGoogle Scholar
  134. Tan PK, Downey TJ, Spitznagel EL Jr, Xu P, Fu D, Dimitrov DS, Lempicki RA, Raaka BM, Cam MC (2003) Evaluation of gene expression measurements from commercial microarray platforms. Nucleic Acids Res 31:5676–5684PubMedCrossRefGoogle Scholar
  135. Tan L, Ehrlich E, Yu XF (2007) DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest. J Virol 81:10822–10830PubMedCrossRefGoogle Scholar
  136. Tibshirani R, Hastie T, Eisen M, al. e (1999) Clustering methods for the analysis of DNA microarray data. Technical report. Stanford University, Stanford, CAGoogle Scholar
  137. 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
  138. Tornatore C, Nath A, Amemiya K, Major EO (1991) Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. J Virol 65:6094–6100PubMedGoogle Scholar
  139. Tornatore C, Chandra R, Berger JR, Major EO (1994) HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44:481–487PubMedGoogle Scholar
  140. Torres-Muñoz J, Stockton P, Tacoronte N, Roberts B, Maronpot RR, Petito CK (2001a) Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection. J Neuropathol Exp Neur 60:885–892Google Scholar
  141. Torres-Muñoz JE, Redondo M, Czeisler C, Roberts B, Tacoronte N, Petito CK (2001b) Upregulation of glial clusterin in brains of patients with AIDs. Brain Res 888:297–301PubMedCrossRefGoogle Scholar
  142. Trillo-Pazos G, Diamanturos A, Rislove L, Menza T, Chao W, Belem P, Sadiq S, Morgello S, Sharer L, Volsky DJ (2003) Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection. Brain Pathol 13:144–154PubMedCrossRefGoogle Scholar
  143. Wang Z, Pekarskaya O, Bencheikh M, Chao W, Gelbard H, Ghorpade A, Rothstein JD, Volsky DJ (2003) Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology 312:60–73PubMedCrossRefGoogle Scholar
  144. Wang Z, Trillo-Pazos G, Kim S-Y, Canki M, Morgello S, Sharer LR, Gelbard HA, Su Z-Z, Kang D-C, Brooks AI, Fisher PB, Volsky DJ (2004) Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis. J Neurovirology 10:25–32Google Scholar
  145. Wang T, Gong N, Liu J, Kadiu I, Kraft-Terry SD, Mosley RL, Volsky DJ, Ciborowski P, Gendelman HE (2008) Proteomic modeling for HIV-1 infected microglia-astrocyte crosstalk. PLoS ONE 3:e2507PubMedCrossRefGoogle Scholar
  146. Werner T (2008) Bioinformatics applications for pathway analysis of microarray data. Curr Opin Biotechnol 19:50–54PubMedCrossRefGoogle Scholar
  147. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA (1986) Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 83:7089–7093PubMedCrossRefGoogle Scholar
  148. Yeung MC, Pulliam L, Lau AS (1995) The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha. AIDS 9:137–143PubMedGoogle Scholar
  149. Yoder K, Sarasin A, Kraemer K, McIlhatton M, Bushman F, Fishel R (2006) The DNA repair genes XPB and XPD defend cells from retroviral infection. Proc Natl Acad Sci USA 103:4622–4627PubMedCrossRefGoogle Scholar
  150. Zhang S, Amstein T, Shen J, Brush FR, Gershenfeld HK (2005) Molecular correlates of emotional learning using genetically selected rat lines. Genes Brain Behav 4:99–109PubMedCrossRefGoogle Scholar
  151. Zhou BY, Liu Y, Kim B, Xiao Y, He JJ (2004) Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes. Mol Cell Neurosci 27:296–305PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Alejandra Borjabad
    • 1
    • 2
  • Andrew I. Brooks
    • 3
  • David J. Volsky
    • 1
    • 2
    • 1
  1. 1.Molecular Virology DivisionSt. Luke’s-Roosevelt Hospital CenterNew YorkUSA
  2. 2.Department of Pathology & Cell BiologyColumbia UniversityNew YorkUSA
  3. 3.Environmental and Occupational Health Science Institute, Department of GeneticsRutgers UniversityPiscatawayUSA

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