Skip to main content

Advertisement

SpringerLink
Log in

Reconstitution of human immunodeficiency virus-induced neurodegeneration using isolated populations of human neurons, astrocytes, and microglia and neuroprotection mediated by insulin-like growth factors

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Primary human neuron cultures are an important in vitro model system for studies on mechanisms involved in human immunodeficiency virus (HIV)-associated dementia (HAD) and other neurological disorders. Here, more than 80 cell surface antigens were screened to identify a marker that could readily distinguish between neurons and astrocytes and found that neurons lack CD44 surface expression, whereas astrocytes and other cell types in brain are CD44+. Neurons and astrocytes were isolated from human fetal brain based on differential expression of CD44. Using purified neurons cocultured with astrocytes and/or microglia, it was demonstrated that HIV infection of microglia induces cellular activation and production of soluble factors that activate uninfected microglia and astrocytes and induce neuronal cell death. Activated astrocytes promoted HIV replication in microglia, thereby amplifying HIV-induced neurotoxicity. A screen for 120 cytokine/proteins detected upregulation of insulin-like growth factor (IGF)-binding protein (IGFBP)-2, interleukin (IL)-6, and CCL8/MCP-2 (monocyte chemoattractant protein 2) in supernatants of HIV-infected brain cell cultures. IGF-1 and -2 increased neuronal survival in HIV-infected brain cell cultures, whereas IGFBP-2 inhibited prosurvival effects of these growth factors. These findings identify CD44 as a marker that can be used to sort neurons from other cell types in brain, suggest the importance of microglia-astrocyte interactions in neurodegenerative mechanisms associated with HIV infection, and indicate a role for insulin-like growth factors in neuroprotection from HIV-induced neurodegeneration. The ability to reconstitute brain cultures using isolated populations of neurons, astrocytes, and microglia will be valuable for studies on pathogenic mechanisms in HAD and other neurological disorders, and will also facilitate neuroactive drug discovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Achim CL, Morey MK, Wiley CA (1991). Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients. AIDS 5: 535–541.

    Article  PubMed  CAS  Google Scholar 

  • Albright AV, Gonzalez-Scarano F (2004). Microarray analysis of activated mixed glial (microglia) and monocytederived macrophage gene expression. J Neuroimmunol 157: 27–38.

    Article  PubMed  CAS  Google Scholar 

  • Albright AV, Shieh JT, Itoh T, Lee B, Pleasure D, O’Connor MJ, Doms RW, Gonzalez-Scarano F (1999). Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates. J Virol 73: 205–213.

    PubMed  CAS  Google Scholar 

  • Anderson CN, Tolkovsky AM (1999). A role for MAPK/ERK in sympathetic neuron survival: protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside. J Neurosci 19: 664–673.

    PubMed  CAS  Google Scholar 

  • Araque A, Carmignoto G, Haydon PG (2001). Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63: 795–813.

    Article  PubMed  CAS  Google Scholar 

  • Baba M, Nishimura O, Kanzaki N, Okamoto M, Sawada H, Iizawa Y, Shiraishi M, Aramaki Y, Okonogi K, Ogawa Y, Meguro K, Fujino M (1999). A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci U S A 96: 5698–5703.

    Article  PubMed  CAS  Google Scholar 

  • Babcock GJ, Mirzabekov T, Wojtowicz W, Sodroski J (2001). Ligand binding characteristics of CXCR4 incorporated into paramagnetic proteoliposomes. J Biol Chem 276: 38433–38440.

    Article  PubMed  CAS  Google Scholar 

  • Bach LA, Headey SJ, Norton RS (2005). IGF-binding proteins—the pieces are falling into place. Trends Endocrinol Metab 16: 228–234.

    Article  PubMed  CAS  Google Scholar 

  • Beck KD, Powell-Braxton L, Widmer HR, Valverde J, Hefti F (1995). Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14: 717–730.

    Article  PubMed  CAS  Google Scholar 

  • Berger EA, Murphy PM, Farber JM (1999). Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17: 657–700.

    Article  PubMed  CAS  Google Scholar 

  • 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 TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4: 702–710.

    Article  PubMed  CAS  Google Scholar 

  • Boven LA, Middel J, Portegies P, Verhoef J, Jansen GH, Nottet HS (1999). Overexpression of nerve growth factor and basic fibroblast growth factor in AIDS dementia complex. J Neuroimmunol 97: 154–162.

    Article  PubMed  CAS  Google Scholar 

  • Brack-Werner R (1999). Astrocytes: HIV cellular reservoirs and important participants in neuropathogenesis. AIDS 13: 1–22.

    Article  PubMed  CAS  Google Scholar 

  • Busciglio J, Lorenzo A, Yeh J, Yankner BA (1995). Betaamyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 14: 879–888.

    Article  PubMed  CAS  Google Scholar 

  • Carrick FE, Forbes BE, Wallace JC (2001). BIAcore analysis of bovine insulin-like growth factor (IGF)-binding protein-2 identifies major IGF binding site determinants in both the amino- and carboxyl-terminal domains. J Biol Chem 276: 27120–27128.

    Article  PubMed  CAS  Google Scholar 

  • Chesik D, De Keyser J, Wilczak N (2004). Involvement of insulin-like growth factor binding protein-2 in activated microglia as assessed in post mortem human brain. Neurosci Lett 362: 14–16.

    Article  PubMed  CAS  Google Scholar 

  • Cichy J, Pure E (2003). The liberation of CD44. J Cell Biol 161: 839–843.

    Article  PubMed  CAS  Google Scholar 

  • Congote LF (2005). Monitoring insulin-like growth factors in HIV infection and AIDS. Clin Chim Acta 361: 30–53.

    Article  PubMed  CAS  Google Scholar 

  • Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR (1997). Change in coreceptor use coreceptor use correlates with disease progression in HIV-1-infected individuals. JExp Med 185: 621–628.

    CAS  Google Scholar 

  • Coughlan CM, McManus CM, Sharron M, Gao Z, Murphy D, Jaffer S, Choe W, Chen W, Hesselgesser J, Gaylord H, Kalyuzhny A, Lee VM, Wolf B, Doms RW, Kolson DL (2000). Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons. Neuroscience 97: 591–600.

    Article  PubMed  CAS  Google Scholar 

  • Courtney MJ, Coffey ET (1999). The mechanism of Ara-C-induced apoptosis of differentiating cerebellar granule neurons. Eur J Neurosci 11: 1073–1084.

    Article  PubMed  CAS  Google Scholar 

  • D’Ambrosio R (2004). The role of glial membrane ion channels in seizures and epileptogenesis. Pharmacol Ther 103: 95–108.

    Article  PubMed  Google Scholar 

  • Davis CW, Doms RW (2004). HIV transmission: closing all the doors. J Exp Med 199: 1037–1040.

    Article  PubMed  CAS  Google Scholar 

  • Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE (2005). Molecular interactions of the IGF system. Cytokine Growth Factor Rev 16: 421–439.

    Article  PubMed  CAS  Google Scholar 

  • Dong Y, Benveniste EN (2001). Immune function of astrocytes. Glia 36: 180–190.

    Article  PubMed  CAS  Google Scholar 

  • Donzella GA, Schols D, Lin SW, Este JA, Nagashima KA, Maddon PJ, Allaway GP, Sakmar TP, Henson G, De Clercq E, Moore JP (1998). AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 4: 72–77.

    Article  PubMed  CAS  Google Scholar 

  • Elmlinger MW, Deininger MH, Schuett BS, Meyermann R, Duffner F, Grote EH, Ranke MB (2001). In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 142: 1652–1658.

    Article  PubMed  CAS  Google Scholar 

  • Firth SM, Baxter RC (2002). Cellular actions of the insulinlike growth factor binding proteins. En docr Rev 23: 824–854.

    CAS  Google Scholar 

  • Gallo P, Frei K, Rordorf C, Lazdins J, Tavolato B, Fontana A (1989). Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. J Neuroimmunol 23: 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Gartner S (2000). HIV infection and dementia. Science 287: 602–604.

    Article  PubMed  CAS  Google Scholar 

  • Genis P, Jett M, Bernton EW, Boyle T, Gelbard HA, Dzenko K, Keane RW, Resnick L, Mizrachi Y, Volsky DJ, et al. (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: 1703–1718.

    Article  PubMed  CAS  Google Scholar 

  • Ghorpade A, Xia MQ, Hyman BT, Persidsky Y, Nukuna A, Bock P, Che M, Limoges J, Gendelman HE, Mackay CR (1998). Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. J Virol 72: 3351–3361.

    PubMed  CAS  Google Scholar 

  • Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM (1998). Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. J Biol Chem 273: 4289–4298.

    Article  PubMed  CAS  Google Scholar 

  • Gong X, Gong W, Kuhns DB, Ben-Baruch A, Howard OM, Wang JM (1997). Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors. J Biol Chem 272: 11682–11685.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Scarano F, Baltuch G (1999). Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22: 219–240.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Scarano F, Martin-Garcia J (2005). The neuropathogenesis of AIDS. Nat Rev Immunol 5: 69–81.

    Article  PubMed  CAS  Google Scholar 

  • Griffioen AW, Coenen MJ, Damen CA, Hellwig SM, van Weering DH, Vooys W, Blijham GH, Groenewegen G (1997). CD44 is involved in tumor angiogenesis; an activation antigen on human endothelial cells. Blood 90: 1150–1159.

    PubMed  CAS  Google Scholar 

  • Gveric D, Cuzner ML, Newcombe J (1999). Insulin-like growth factors and binding proteins in multiple sclerosis plaques. Neuropathol Appl Neurobiol 25: 215–225.

    Article  PubMed  CAS  Google Scholar 

  • Haigwood NL (2004). Predictive value of primate models for AIDS. AIDS Rev 6: 187–198.

    PubMed  Google Scholar 

  • Haughey NJ, Cutler RG, Tamara A, McArthur JC, Vargas DL, Pardo CA, Turchan J, Nath A, Mattson MP (2004). Perturbation of sphingolipid metabolism and ceramide production in HIV-dementia. Ann Neurol 55: 257–267.

    Article  PubMed  CAS  Google Scholar 

  • He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, Busciglio J, Yang X, Hofmann W, Newman W, Mackay CR, Sodroski J, Gabuzda D (1997). CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 385: 645–649.

    Article  PubMed  CAS  Google Scholar 

  • Hesselgesser J, Taub D, Baskar P, Greenberg M, Hoxie J, Kolson DL, Horuk R (1998). Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4. Curr Biol 8: 595–598.

    Article  PubMed  CAS  Google Scholar 

  • Hori K, Burd PR, Kutza J, Weih KA, Clouse KA (1999). Human astrocytes inhibit HIV-1 expression in monocytederived macrophages by secreted factors. AIDS 13: 751–758.

    Article  PubMed  CAS  Google Scholar 

  • Jain S, Golde DW, Bailey R, Geffner ME (1998). Insulin-like growth factor-I resistance. Endocr Rev 19: 625–646.

    Article  PubMed  CAS  Google Scholar 

  • Jiang H, Van De Ven C, Satwani P, Baxi LV, Cairo MS (2004). Differential gene expression patterns by oligonucleotide microarray of basal versus lipopolysaccharide-activated monocytes from cord blood versus adult peripheral blood. J Immunol 172: 5870–5879.

    PubMed  CAS  Google Scholar 

  • Kaul M, Garden GA, Lipton SA (2001). Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410: 988–994.

    Article  PubMed  CAS  Google Scholar 

  • Kaul M, Lipton SA (1999). Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci U S A 96: 8212–8216.

    Article  PubMed  CAS  Google Scholar 

  • Keyoung HM, Roy NS, Benraiss A, Louissaint A Jr, Suzuki A, Hashimoto M, Rashbaum WK, Okano H, Goldman SA (2001). High-yield selection and extraction of two promoter-defined phenotypes of neural stem cells from the fetal human brain. Nat Biotechnol 19: 843–850.

    Article  PubMed  CAS  Google Scholar 

  • Klasse PJ, Moore JP (2004). Is there enough gp120 in the body fluids of HIV-1-infected individuals to have biologically significant effects? Virology 323: 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Klein RS, Williams KC, Alvarez-Hernandez X, Westmoreland S, Force T, Lackner AA, Luster AD (1999). Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J Immunol 163: 1636–1646.

    PubMed  CAS  Google Scholar 

  • Konishi Y, Lindholm K, Yang LB, Li R, Shen Y (2002). Isolation of living neurons from human elderly brains using the immunomagnetic sorting DNA-linker system. Am J Pathol 161: 1567–1576.

    Article  PubMed  CAS  Google Scholar 

  • Laue L, Pizzo PA, Butler K, Cutler GB Jr (1990). Growth and neuroendocrine dysfunction in children with acquired immunodeficiency syndrome. J Pediatr 117: 541–545.

    Article  PubMed  CAS  Google Scholar 

  • Mackay CR, Terpe HJ, Stauder R, Marston WL, Stark H, Gunthert U (1994). Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 124: 71–82.

    Article  PubMed  CAS  Google Scholar 

  • Mackay KB, Loddick SA, Naeve GS, Vana AM, Verge GM, Foster AC (2003). Neuroprotective effects of insulin-like growth factor-binding protein ligand inhibitors in vitro and in vivo. J Cereb Blood Flow Metab 23: 1160–1167.

    Article  PubMed  CAS  Google Scholar 

  • McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, Sacktor N (2003). Human immunodeficiency virus-associated dementia: an evolving disease. J NeuroVirol 9: 205–221.

    PubMed  CAS  Google Scholar 

  • Merrill JE, Chen IS (1991). HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J 5: 2391–2397.

    PubMed  CAS  Google Scholar 

  • Messadi DV, Bertolami CN (1993). CD44 and hyaluronan expression in human cutaneous scar fibroblasts. Am J Pathol 142: 1041–1049.

    PubMed  CAS  Google Scholar 

  • Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ (1998). Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A 95: 14500–14505.

    Article  PubMed  CAS  Google Scholar 

  • Miller G (2005). The dark side of glia. Science 308: 778–781.

    Article  PubMed  CAS  Google Scholar 

  • Mrak RE, Griffin WS (2005). Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26: 349–354.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima K, Martinez-Maza O, Hirano T, Breen EC, Nishanian PG, Salazar-Gonzalez JF, Fahey JL, Kishimoto T (1989). Induction of IL-6 (B cell stimulatory factor-2/IFN-beta 2) production by HIV. J Immunol 142: 531–536.

    PubMed  CAS  Google Scholar 

  • Nottet HS, Jett M, Flanagan CR, Zhai QH, Persidsky Y, Rizzino A, Bernton EW, Genis P, Baldwin T, Schwartz J, et al. (1995). A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, plateletactivating factor, and tumor necrosis factor-alpha by activated HIV-1-infected monocytes is attenuated by primary human astrocytes. J Immunol 154: 3567–3581.

    PubMed  CAS  Google Scholar 

  • O’Donnell SL, Frederick TJ, Krady JK, Vannucci SJ, Wood TL (2002). IGF-I and microglia/macrophage proliferation in the ischemic mouse brain. Glia 39: 85–97.

    Article  PubMed  Google Scholar 

  • Ohagen A, Ghosh S, He J, Huang K, Chen Y, Yuan M, Osathanondh R, Gartner S, Shi B, Shaw G, Gabuzda D (1999). Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope. J Virol 73: 897–906.

    PubMed  CAS  Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994). Glutamate-mediated astrocyteneuron signalling. Nature 369: 744–747.

    Article  PubMed  CAS  Google Scholar 

  • Perrella O, Carrieri PB, Guarnaccia D, Soscia M (1992). Cerebrospinal fluid cytokines in AIDS dementia complex. J Neurol 239: 387–388.

    PubMed  CAS  Google Scholar 

  • Persidsky Y, Buttini M, Limoges J, Bock P, Gendelman HE (1997). An analysis of HIV-1-associated inflammatory products in brain tissue of humans and SCID mice with HIV-1 encephalitis. J Neurovirol 3: 401–416.

    Article  PubMed  CAS  Google Scholar 

  • Petito CK, Roberts B (1995). Evidence of apoptotic cell death in HIV encephalitis. Am J Pathol 146: 1121–11230.

    PubMed  CAS  Google Scholar 

  • Ponta H, Sherman L, Herrlich PA (2003). CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4: 33–45.

    Article  PubMed  CAS  Google Scholar 

  • Power C, Patel KD (2004). Neurolipidomics: an inflammatory perspective on fat in the brain. Neurology 63: 608–609.

    PubMed  Google Scholar 

  • Price RW (1996). Neurological complications of HIV infection. Lancet 348: 445–452.

    Article  PubMed  CAS  Google Scholar 

  • Proost P, Wuyts A, Van Damme J (1996). Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1. J Leukoc Biol 59: 67–74.

    PubMed  CAS  Google Scholar 

  • Rajaram S, Baylink DJ, Mohan S (1997). Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 18: 801–831.

    Article  PubMed  CAS  Google Scholar 

  • Rondanelli M, Caselli D, Arico M, Maccabruni A, Magnani B, Bacchella L, De Stefano A, Maghnie M, Solerte SB, Minoli L (2002). Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 response to growth hormone is impaired in HIV-infected children. AIDS Res Hum Retroviruses 18: 331–339.

    Article  PubMed  CAS  Google Scholar 

  • Rossio JL, Esser MT, Suryanarayana K, Schneider DK, Bess JW, Jr., Vasquez GM, Wiltrout TA, Chertova E, Grimes MK, Sattentau Q, Arthur LO, Henderson LE, Lifson JD (1998). Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol 72: 7992–8001.

    PubMed  CAS  Google Scholar 

  • Sabri F, Titanji K, De Milito A, Chiodi F (2003). Astrocyte activation and apoptosis: their roles in the neuropathology of HIV infection. Brain Pathol 13: 84–94.

    Article  PubMed  Google Scholar 

  • Sabri F, Tresoldi E, Di Stefano M, Polo S, Monaco MC, Verani A, Fiore JR, Lusso P, Major E, Chiodi F, Scarlatti G (1999). Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors. Virology 264: 370–384.

    Article  PubMed  CAS  Google Scholar 

  • Sawamoto K, Nakao N, Kobayashi K, Matsushita N, Takahashi H, Kakishita K, Yamamoto A, Yoshizaki T, Terashima T, Murakami F, Itakura T, Okano H (2001). Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons. Proc Natl Acad Sci U S A 98: 6423–6428.

    Article  PubMed  CAS  Google Scholar 

  • Schols D, Struyf S, Van Damme J, Este JA, Henson G, De Clercq E (1997). Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J Exp Med 186: 1383–1388.

    Article  PubMed  CAS  Google Scholar 

  • Shi B, De Girolami U, He J, Wang S, Lorenzo A, Busciglio J, Gabuzda D (1996). Apoptosis induced by HIV-1 infection of the central nervous system. J Clin Invest 98: 1979–1990.

    Article  PubMed  CAS  Google Scholar 

  • Stewart CE, Rotwein P (1996). Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76: 1005–1026.

    PubMed  CAS  Google Scholar 

  • Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong HY, Sakai J, Yamashita T, Nukiwa T, Matsushima K (2000). Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. Blood 96: 2584–2591.

    PubMed  CAS  Google Scholar 

  • Sy MS, Mori H, Liu D (1997). CD44 as a marker in human cancers. Curr Opin Oncol 9: 108–112.

    Article  PubMed  CAS  Google Scholar 

  • Trentin L, Garbisa S, Zambello R, Agostini C, Caenazzo C, Di Francesco C, Cipriani A, Francavilla E, Semenzato G (1992). Spontaneous production of interleukin-6 by alveolar macrophages from human immunodeficiency virus type 1-infected patients. J Infect Dis 166: 731–737.

    Article  PubMed  CAS  Google Scholar 

  • Trubey CM, Chertova E, Coren LV, Hilburn JM, Hixson CV, Nagashima K, Lifson JD, Ott DE (2003). Quantitation of HLA class II protein incorporated into human immunodeficiency type 1 virions purified by anti-CD45 immunoaffinity depletion of microvesicles. J Virol 77: 12699–12709.

    Article  PubMed  CAS  Google Scholar 

  • Vallat AV, De Girolami U, He J, Mhashilkar A, Marasco W, Shi B, Gray F, Bell J, Keohane C, Smith TW, Gabuzda D (1998). Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. Am J Pathol 152: 167–178.

    PubMed  CAS  Google Scholar 

  • van Maanen M, Sutton RE (2003). Rodent models for HIV-1 infection and disease. Curr HIV Res 1: 121–130.

    Article  PubMed  Google Scholar 

  • Verani A, Pesenti E, Polo S, Tresoldi E, Scarlatti G, Lusso P, Siccardi AG, Vercelli D (1998). CXCR4 is a functional coreceptor for infection of human macrophages by CXCR4-dependent primary HIV-1 isolates. J Immunol 161: 2084–2088.

    PubMed  CAS  Google Scholar 

  • Wang J, Babcock GJ, Choe H, Farzan M, Sodroski J, Gabuzda D (2004). N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. Virology 324: 140–150.

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Crawford K, Yuan M, Wang H, Gorry PR, Gabuzda D (2002). Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines. J Infect Dis 185: 885–897.

    Article  PubMed  CAS  Google Scholar 

  • Wasmuth JC, Nischalke HD, Jutte A, Fatkenheuer G, Salzberger B, Sauerbruch T, Spengler U, Rockstroh JK, Dumoulin FL (2004). Chemokine mRNA levels in mononucleated cells of HIV-infected patients before and after initiation of PI-versus NNRTI-containing HAART. Antiviral Res 61: 207–212.

    Article  PubMed  CAS  Google Scholar 

  • White MG, Hammond RR, Sanders VJ, Bonaroti EA, Mehta AP, Wang G, Wiley CA, Achim CL (1999). Neuronenriched second trimester human cultures: growth factor response and in vivo graft survival. Cell Transplant 8: 59–73.

    PubMed  CAS  Google Scholar 

  • Woelk CH, Ottones F, Plotkin CR, Du P, Royer CD, Rought SE, Lozach J, Sasik R, Kornbluth RS, Richman DD, Corbeil J (2004). Interferon gene expression following HIV type 1 infection of monocyte-derived macrophages. AIDS Res Hum Retroviruses 20: 1210–1222.

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA (2002). Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med 8: 600–606.

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Kulkosky J, Acheampong E, Nunnari G, Sullivan J, Pomerantz RJ (2004). HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy. Proc Natl Acad Sci U S A 101: 7070–7075.

    Article  PubMed  CAS  Google Scholar 

  • Yang OO, Garcia-Zepeda EA, Walker BD, Luster AD (2002). Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5. J Infect Dis 185: 1174–1178.

    Article  PubMed  CAS  Google Scholar 

  • Ying Wang J, Peruzzi F, Lassak A, Del Valle L, Radhakrishnan S, Rappaport J, Khalili K, Amini S, Reiss K (2003). Neuroprotective effects of IGF-I against TNFalphainduced neuronal damage in HIV-associated dementia. Virology 305: 66–76.

    Article  Google Scholar 

  • Zhang W, Wang H, Song SW, Fuller GN (2002). Insulinlike growth factor binding protein 2: gene expression microarrays and the hypothesis-generation paradigm. Brain Pathol 12: 87–94.

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Champagne N, Beitel LK, Goodyer CG, Trifiro M, LeBlanc A (2004). Estrogen and androgen protection of human neurons against intracellular amyloid beta1-42 toxicity through heat shock protein 70. J Neurosci 24: 5315–5321.

    Article  PubMed  CAS  Google Scholar 

  • Zheng J, Thylin MR, Ghorpade A, Xiong H, Persidsky Y, Cotter R, Niemann D, Che M, Zeng YC, Gelbard HA, Shepard RB, Swartz JM, Gendelman HE (1999). Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol 98: 185–200.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, JF 816, 44 Binney Street, 02115, MA, USA

    Jianbin Wang & Dana Gabuzda

  2. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA

    Jianbin Wang

  3. Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA

    Jianbin Wang & Dana Gabuzda

Authors
  1. Jianbin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dana Gabuzda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dana Gabuzda.

Additional information

This work was supported by National Institutes of Health grant NS35734 and NS37277. Core facilities were supported by a Center for AIDS Research grant and DFCI/Harvard Center for Cancer Research grant.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Gabuzda, D. Reconstitution of human immunodeficiency virus-induced neurodegeneration using isolated populations of human neurons, astrocytes, and microglia and neuroprotection mediated by insulin-like growth factors. Journal of NeuroVirology 12, 472–491 (2006). https://doi.org/10.1080/13550280601039659

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280601039659

Keywords

Search

Navigation