Journal of NeuroVirology

, Volume 8, Issue 6, pp 585–598 | Cite as

Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia

  • R. Cotter
  • C. Williams
  • L. Ryan
  • David Erichsen
  • A. Lopez
  • H. Peng
  • J. Zheng
Article

Abstract

Leukocyte migration and activation play an important role in immune surveillance and the pathogenesis of a variety of neurodegenerative disorders, including human immunodeficiency virus (HIV)-1-associated dementia (HAD). A novel chemokine named fractalkine (FKN, CX3CL1), which exists in both membrane-anchored and soluble isoforms, has been proposed to participate in the generation and progression of inflammatory brain disorders. Upon binding to the CX3C receptor one (CX3CR1), FKN induces adhesion, chemoattraction, and activation of leukocytes, including brain macrophages and microglia (MP). Constitutively expressed in the central nervous system (CNS), mainly by neurons, FKN is up-regulated and released in response to proinflammatory stimuli. Importantly, FKN is up-regulated in the brain tissue and cerebrospinal fluid (CSF) of HAD patients. Together, these observations suggest that FKN and its receptor have a unique role in regulating the neuroinflammatory events underlying disease. This review will examine how FKN contributes to the recruitment and activation of CX3CR1-expressing MP, which are critical events in the neuropathogenesis of HAD.

Keywords

chemokine receptors chemokines fractalkine HIV-1—associated dementia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996). Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274: 1917–1926.PubMedCrossRefGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. Alexander RW (2001). Cytokine receptor CX3CR-1 and fractalkine: new factors in the atherosclerosis drama? CircRes 89: 376–377.Google Scholar
  4. Aquaro S, Panti S, Caroleo MC, Balestra E, Cenci A, Forbici F, Ippolito G, Mastino A, Testi R, Mollace V, et al (2000). Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. J Leukoc Biol 68: 429–435.PubMedGoogle Scholar
  5. Asare E, Dunn G, Glass J, McArthur J, Luthert P, Lantos P, Everall I (1996). Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Am J Pathol 148: 31–38.PubMedGoogle Scholar
  6. Baggiolini M, Dewald B, Moser B (1997). Human chemokines: an update. Annu Rev Immunol 15: 675–705.PubMedCrossRefGoogle Scholar
  7. Barnea A, Aguila-Mansilla N, Chute HT, Welcher AA (1996). Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains. Brain Res 732: 52–60.PubMedCrossRefGoogle Scholar
  8. Batchelor PE, Liberatore GT, Wong JY, Porritt MJ, Frerichs F, Donnan GA, Howells DW (1999). Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 19: 1708–1716.PubMedGoogle Scholar
  9. Bazan J, Bacon K, Hardiman G, Wang W, Soo K, Rossi D, Greaves D, Zlotnik A, Schall T (1997). A new class of membrane-bound chemokine with a CX3C motif. Nature 385: 640–644.PubMedCrossRefGoogle Scholar
  10. Biber K, Sauter A, Brouwer N, Copray SC, Boddeke HW (2001). Ischemia-induced neuronal expression of the microglia attracting chemokine secondary lymphoid-tissue chemokine (SLC). Glia 34: 121–133.PubMedCrossRefGoogle Scholar
  11. Boehme SA, Lio FM, Maciejewski-Lenoir D, Bacon KB, Conlon PJ (2000). The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia. J Immunol 165: 397–403.PubMedGoogle Scholar
  12. Broder CC, Collman RG (1997). Chemokine receptors and HIV. J Leukoc Biol 62: 20–29.PubMedGoogle Scholar
  13. Cambien B, Pomeranz M, Schmid-Antomarchi H, Millet MA, Breittmayer V, Rossi B, Schmid-Alliana A (2001). Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion. Blood 97: 2031–2037.PubMedCrossRefGoogle Scholar
  14. Caroleo MC, Costa N, Bracci-Laudiero L, Aloe L (2001). Human monocyte/macrophages activated by exposure to LPS overexpress NGF and NGF receptors. J Neuroimmunol 113: 193–201.PubMedCrossRefGoogle Scholar
  15. Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, et al (2000). Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA 283: 381–390.PubMedCrossRefGoogle Scholar
  16. Chao CC, Hu S, Sheng WS, Tsang M, Peterson PK (1995). Tumor necrosis factor-α mediates the release of bioactive transforming growth factor β in murine microglial cell cultures. Clin Immunol Immunopathol 77: 358–365.PubMedCrossRefGoogle Scholar
  17. Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ (2000a). Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci (Online) 20: RC87.Google Scholar
  18. Chapman GA, Moores KE, Gohil J, Berkhout TA, Patel L, Green P, Macphee CH, Stewart BR (2000b). The role of fractalkine in the recruitment of monocytes to the endothelium. Eur J Pharmacol 392: 189–195.PubMedCrossRefGoogle Scholar
  19. Cockwell P, Chakravorty SJ, Girdlestone J, Savage CO (2002). Fractalkine expression in human renal inflammation. J Pathol 196: 85–90.PubMedCrossRefGoogle Scholar
  20. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (1998). Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. J Biol Chem 273: 23799–23804.PubMedCrossRefGoogle Scholar
  21. 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 Tatstimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci USA 95: 3117–3121.PubMedCrossRefGoogle Scholar
  22. Cook DN, Chen SC, Sullivan LM, Manfra DJ, Wiekowski MT, Prosser DM, Vassileva G, Lira SA (2001). Generation and analysis of mice lacking the chemokine fractalkine. Mol Cell Biol 21: 3159–3165.PubMedCrossRefGoogle Scholar
  23. Cotter R, Zheng J, Gendelman HE (1999a). The role of mononuclear phagocytes in neurodegenerative disorders: lessons from multiple sclerosis, Alzheimer’s disease and HIV-1 dementia. In: Advances in neurodegenerative disorders. Marwah J, Teitelbaum H (eds). Prominent Press: Scottsdale, AZ, pp 203–241.Google Scholar
  24. Cotter R, Zheng J, Niemann D, Thomas E, Gendelman H (1999b). CD40L activation of mononuclear phagocytes: regulation of HIV-1 replication and beta-chemokine production. Paper presented at XIth International Congress of Virology, Interbational Union of Microbiological Societies, Sydney, Australia, August 9–13.Google Scholar
  25. Cotter RL, Zheng J, Che M, Niemann D, Liu Y, He J, Thomas E, Gendelman HE (2001). Regulation of human immunodeficiency virus type 1 infection, beta chemokine production, and CCR5 expression in CD40L-stimulated macrophages: immune control of viral entry. J Virol 75: 4308–4320.PubMedCrossRefGoogle Scholar
  26. Coughlan CM, McManus CM, Sharron M, Gao Z, Murphy D, Jaffer S, Choe W, Chen W, Hesselgesser J, Gaylord H, et al (2000). Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons [In Process Citation]. Neuroscience 97: 591–600.PubMedCrossRefGoogle Scholar
  27. Desbaillets I, Tada M, de Tribolet N, Diserens AC, Hamou MF, Van Meir EG (1994). Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. Int J Cancer 58: 240–247.PubMedCrossRefGoogle Scholar
  28. Deshmukh M, Vasilakos J, Deckwerth TL (1996). Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases. J Cell Biol 135: 1341–1354.PubMedCrossRefGoogle Scholar
  29. Devi LA (2000). G-protein-coupled receptor dimers in the lime light. Trends Pharmacol Sci 21: 324–326.PubMedCrossRefGoogle Scholar
  30. Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Harter P, Norgauer J (2001). Fractalkine induces chemotaxis and actin polymerization in human dendritic cells. Inflamm Res 50: 529–533.PubMedCrossRefGoogle Scholar
  31. Dickson D, Lee S, Hatch W, Mattiace L, Brosnan C, Lyman W (1994). Macrophages and microglia in HIV-related CNS neuropathology. In: HIV, AIDS, and the brain. Price R, Perry S (eds). Raven: New York, pp 99–118.Google Scholar
  32. Dorf ME, Berman MA, Tanabe S, Heesen M, Luo Y (2000). Astrocytes express functional chemokine receptors. J Neuroimmunol 111: 109–121.PubMedCrossRefGoogle Scholar
  33. Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA (1996). HIV-1 entry into CD4+ cells is mediated by the chemokines receptor CC-CKR-5. Nature 381: 667–673.PubMedCrossRefGoogle Scholar
  34. Elkabes S, DiCicco-Bloom EM, Black IB (1996). Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16: 2508–2521.PubMedGoogle Scholar
  35. Endres MJ, Clapham PR, Marsh M, Ahuja M, Turner JD, McKnight A, Thomas JF, Stoebenau-Haggarty B, Choe S, Vance PJ, et al (1996). CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87: 745–756.PubMedCrossRefGoogle Scholar
  36. Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debre P, et al (2000). Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1. Science 287: 2274–2277.PubMedCrossRefGoogle Scholar
  37. Feng L, Chen S, Garcia GE, Xia Y, Siani MA, Botti P, Wilson CB, Harrison JK, Bacon KB (1999). Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX3CR1 rapid communication. Kidney Int 56: 612–620.PubMedCrossRefGoogle Scholar
  38. Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L’Heureux D, Regulier EG, Richardson MW, Amini S, Morgello S, Khalili K, Rappaport J (2001). CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J NeuroVirol 7: 528–541.PubMedCrossRefGoogle Scholar
  39. Fong AM, Erickson HP, Zachariah JP, Poon S, Schamberg NJ, Imai T, Patel DD (2000). Ultrastructure and function of the fractalkine mucin domain in CX(3)C chemokine domain presentation. J Biol Chem 275: 3781–3786.PubMedCrossRefGoogle Scholar
  40. Fong AM, Robinson LA, Steeber DA, Tedder TF, Yoshie O, Imai T, Patel DD (1998). Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med 188: 1413–1419.PubMedCrossRefGoogle Scholar
  41. Foussat A, Bouchet-Delbos L, Berrebi D, Durand-Gasselin I, Coulomb-L’Hermine A, Krzysiek R, Galanaud P, Levy Y, Emilie D (2001). Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients. Blood 98: 1678–1686.PubMedCrossRefGoogle Scholar
  42. Foussat A, Coulomb-L’Hermine A, Gosling J, Krzysiek R, Durand-Gasselin I, Schall T, Balian A, Richard Y, Galanaud P, Emilie D (2000). Fractalkine receptor expression by T lymphocyte subpopulations and in vivo production of fractalkine in human. Eur J Immunol 30: 87–97.PubMedCrossRefGoogle Scholar
  43. Fraticelli P, Sironi M, Bianchi G, D’Ambrosio D, Albanesi C, Stoppacciaro A, Chieppa M, Allavena P, Ruco L, Girolomoni G, et al (2001). Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest 107: 1173–1181.PubMedCrossRefGoogle Scholar
  44. Fujimoto K, Imaizumi T, Yoshida H, Takanashi S, Okumura K, Satoh K (2001). Interferon-gamma stimulates fractalkine expression in human bronchial epithelial cells and regulates mononuclear cell adherence. Am J Respir Cell Mol Biol 25: 233–238.PubMedGoogle Scholar
  45. Furuichi K, Wada T, Iwata Y, Sakai N, Yoshimoto K, Shimizu M, Kobayashi K, Takasawa K, Kida H, Takeda S, et al (2001). Upregulation of fractalkine in human crescentic glomerulonephritis. Nephron 87: 314–320.PubMedCrossRefGoogle Scholar
  46. Gabuzda D, He J, Ohagen A, Vallat A (1998). Chemokine receptors in HIV-1 infection of the central nervous system. Immunology 10: 203–213.Google Scholar
  47. Gabuzda D, Wang J (1999). Chemokine receptors and virus entry in the central nervous system. J NeuroVirol 5: 643–658.PubMedCrossRefGoogle Scholar
  48. Gabuzda D, Wang J (2000). Chemokine receptors andmechanisms of cell death in HIV neuropathogenesis. J NeuroVirol 6 (Suppl 1): S24-S32.PubMedGoogle Scholar
  49. Gabuzda D, Wang J, Gorry P (2002). HIV-1-associated dementia. In: Chemokines and the nervous system. Ransohoff RM, Suzuki K, Proudfoot AEI, Hickey WF, Harrison JK (eds). Elsevier Science: Amsterdam, pp 345–360.Google Scholar
  50. Garaci E, Caroleo MC, Aloe L, Aquaro S, Piacentini M, Costa N, Amendola A, Micera A, Calio R, Perno CF, Levi-Montalcini R (1999). Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV. Proc Natl Acad Sci USA 96: 14013–14018.PubMedCrossRefGoogle Scholar
  51. Garcia GE, Xia Y, Chen S, Wang Y, Ye RD, Harrison JK, Bacon KB, Zerwes HG, Feng L (2000). NF-kappaB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1beta, TNF-alpha, and LPS. J Leukoc Biol 67: 577–584.PubMedGoogle Scholar
  52. Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW (2001). Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). J Biol Chem 276: 37993–38001.PubMedGoogle Scholar
  53. Gelbard H, Nottet H, Dzenko K, Jett M, Genis P, White R, Wang L, Choi Y-B, Zhang D, Lipton S, et al (1994). Platelet-activating factor: a candidate human immunodeficiency virus type-1 infection neurotoxin. J Virol 68: 4628–4635.PubMedGoogle Scholar
  54. Gelbard HA, Epstein LG (1995). HIV-1 encephalopathy in children. Curr Opin Pediatr 7: 655–662.PubMedGoogle Scholar
  55. Gendelman H, Persidsky Y, Ghorpade A, Limoges J, Stins M, Fiala M, Morrisett R (1997). The neuropathogenesis of AIDS dementia complex. AIDS 11: S35-S45.PubMedCrossRefGoogle Scholar
  56. Gendelman HE (1997). The neuropathogenesis of HIV-1 dementia. In: The neurology of AIDS. Gendelman HE, Lipton SA, Epstein LG, Swindells S (eds). Chapman and Hall: New York, pp 1–10.Google Scholar
  57. Genis P, Jett M, Bernton E, Boyle T, Gelbard H, Dzenko K, Keane R, Resnick L, Mizrachi Y, Volsky D, 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.PubMedCrossRefGoogle Scholar
  58. Ghorpade A, Xia MQ, Hyman BT, Persidsky Y, Nukuna A, Bock P, Che M, Limoges J, Gendelman HE, Mackay CR (1998). Role of the β-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia. J Virol 72: 3351–3361.PubMedGoogle Scholar
  59. Giulian D, Noonan C, Vaca K (1990). HIV-1 infected mononuclear phagocytes release neurotoxins. Science 250: 1593–1595.PubMedCrossRefGoogle Scholar
  60. Giulian D, Yu J, Xia L, Tom D, Li J, Lin SN, Schwarz R, Noonan C (1996). Study of receptor-mediated neurotoxins released by HIV-1 infected mononuclear phagocytes found in human brain. J Neurosci 16: 3139–3153.PubMedGoogle Scholar
  61. Glass JD, Fedor H, Wesselingh SL, McArthur JC (1995). Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol 38: 755–762.PubMedCrossRefGoogle Scholar
  62. Gleichmann M, Gillen C, Czardybon M, Bosse F, Greiner-Petter R, Auer J, Muller HW (2000). Cloning and characterization of SDF-1gamma, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system. Eur J Neurosci 12: 1857–1866.PubMedCrossRefGoogle Scholar
  63. Goda S, Imai T, Yoshie O, Yoneda O, Inoue H, Nagano Y, Okazaki T, Imai H, Bloom ET, Domae N, Umehara H (2000). CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrindependent and -independent mechanisms. J Immunol 164: 4313–4320.PubMedGoogle Scholar
  64. Greaves DR, Hakkinen T, Lucas AD, Liddiard K, Jones E, Quinn CM, Senaratne J, Green FR, Tyson K, Boyle J, et al (2001). Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine are expressed in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 21: 923–929.PubMedGoogle Scholar
  65. Greaves DR, Gordon S (2001). Immunity, atherosclerosis and cardiovascular disease. Trends Immunol 22: 180–181.PubMedCrossRefGoogle Scholar
  66. Harrison JK, Fong AM, Swain PA, Chen S, Yu YR, Salafranca MN, Greenleaf WB, Imai T, Patel DD (2001). Mutational analysis of the fractalkine chemokine domain: basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion. J Biol Chem 276: 8.CrossRefGoogle Scholar
  67. Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA, et al (1998). Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95: 10896–10901.PubMedCrossRefGoogle Scholar
  68. Haskell CA, Cleary MD, Charo IF (1999). Molecular uncoupling of fractalkine-mediated cell adhesion and signal transduction. Rapid flow arrest of CX3CR1-expressing cells is independent of G-protein activation. J Biol Chem 274: 10053–10058.PubMedCrossRefGoogle Scholar
  69. Haskell CA, Cleary MD, Charo IF (2000). Unique role of the chemokine domain of fractalkine in cell capture. Kinetics of receptor dissociation correlate with cell adhesion. J Biol Chem 275: 34183–34189.PubMedCrossRefGoogle Scholar
  70. Haskell CA, Hancock WW, Salant DJ, Gao W, Csizmadia V, Peters W, Faia K, Fituri O, Rottman JB, Charo IF (2001). Targeted deletion of CX(3)CR1 reveals a role for fractalkine in cardiac allograft rejection. J Clin Invest 108: 679–688.PubMedGoogle Scholar
  71. He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, Busciglio J, Yang X, Hofmann W, Newman W, et al (1997). CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 385: 645–649.PubMedCrossRefGoogle Scholar
  72. Hesselgesser J, Horuk R (1999). Chemokine and chemokine receptor expression in the central nervous system. J NeuroVirol 5: 13–26.PubMedCrossRefGoogle Scholar
  73. Heyes MP, Brew BB, Martin A, Price RW, Salazar A, Sidtis JJ, Yergey JA, Mouradian MM, Sadler AE, Keilp J, et al (1991). Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 29: 202–209.PubMedCrossRefGoogle Scholar
  74. Hoover DM, Mizoue LS, Handel TM, Lubkowski J (2000). The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement. J Biol Chem 275: 23187–23193.PubMedCrossRefGoogle Scholar
  75. Horuk R, Martin A, Hesselgesser J, Hadley T, Lu ZH, Wang ZX, Peiper SC (1996). The Duffy antigen receptor for chemokines: structural analysis and expression in the brain. J Leukoc Biol 59: 29–38.PubMedGoogle Scholar
  76. Hughes PM, Botham MS, Frentzel S, Mir A, Perry VH (2002). Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. Glia 37: 314–327.PubMedCrossRefGoogle Scholar
  77. Iismaa T, Biden T, Shine J (1995). G protein-coupled receptors. RG Landes: Austin, TX.Google Scholar
  78. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (1997). Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91: 521–530.PubMedCrossRefGoogle Scholar
  79. Imaizumi T, Matsumiya T, Fujimoto K, Okamoto K, Cui X, Ohtaki U, Hidemi Yoshida, Satoh K (2000). Interferon-gamma stimulates the expression of CX3CL1/fractalkine in cultured human endothelial cells. Tohoku J Exp Med 192: 127–139.PubMedCrossRefGoogle Scholar
  80. Inngjerdingen M, Damaj B, Maghazachi AA (2001). Expression and regulation of chemokine receptors in human natural killer cells. Blood 97: 367–375.PubMedCrossRefGoogle Scholar
  81. Janssen R, Cornblath D, Epstein L, Foa R, McArthur J, Price R, Asbury A, Beckett A, Benson D, Bridge T, et al (1991). Nomenclature and research case definitions for neurological manifestations of human immunodeficiency virus type 1 (HIV-1) infection. Neurology 41: 778–785.Google Scholar
  82. Jiang Z, Piggee C, Heyes MP, Murphy C, Quearry B, Bauer M, Zheng J, Gendelman HE, Markey SP (2001). Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages. J Neuroimmunol 117: 97–107.PubMedCrossRefGoogle Scholar
  83. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR (2000). Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20: 4106–4114.PubMedCrossRefGoogle Scholar
  84. Kansra V, Groves C, Gutierrez-Ramos JC, Polakiewicz RD (2001). Phosphatidylinositol 3-kinase-dependent extracellular calcium influx is essential for CX(3)CR1-mediated activation of the mitogen-activated protein kinase cascade. J Biol Chem 276: 31831–31838.PubMedCrossRefGoogle Scholar
  85. Karpus WJ (2001). Chemokines and central nervous system disorders. J NeuroVirol 7: 493–500.PubMedCrossRefGoogle Scholar
  86. Kaul M, Lipton SA (1999). Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis [In Process Citation]. Proc Natl Acad Sci USA 96: 8212–8216.PubMedCrossRefGoogle Scholar
  87. Kelder W, McArthur JC, Nance-Sproson T, McClernon D, Griffin DE (1998). β-Chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann Neurol 44: 831–835.PubMedCrossRefGoogle Scholar
  88. Kerr SJ, Armati PJ, Guillemin GJ, Brew BJ (1998). Chronic exposure of human neurons to quinolinic acid results in neuronal changes consistent with AIDS dementia complex. AIDS 12: 355–363.PubMedCrossRefGoogle Scholar
  89. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, et al (1999). Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189: 865–870.PubMedCrossRefGoogle Scholar
  90. Kitai R, Zhao ML, Zhang N, Hua LL, Lee SC (2000). Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta. J Neuroimmunol 110: 230–239.PubMedCrossRefGoogle Scholar
  91. Klein R, Williams K, Alvarez-Hernandez X, Westmoreland S, Force T, Lackner A, Luster A (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.PubMedGoogle Scholar
  92. Koenig S, Gendelman HE, Orenstein JM, Canto MCD, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS (1986). Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233: 1089–1093.PubMedCrossRefGoogle Scholar
  93. Kornbluth RS, Kee K, Richman DD (1998). CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta-chemokines. Proc Natl Acad Sci USA 95: 5205–5210.PubMedCrossRefGoogle Scholar
  94. Krebs FC, Ross H, McAllister J, Wigdahl B (2000). HIV-1-associated central nervous system dysfunction. Adv Pharmacol 49: 315–385.PubMedCrossRefGoogle Scholar
  95. Kullander K, Kylberg A, Ebendal T (1997). Specificity of neurotrophin-3 determined by loss-of-function mutagenesis. J Neurosci Res 50: 496–503.PubMedCrossRefGoogle Scholar
  96. Kutsch O, Oh J, Nath A, Benveniste EN (2000). Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol 74: 9214–9221.PubMedCrossRefGoogle Scholar
  97. Lavi E, Strizki JM, Ulrich AM, Zhang W, Fu L, Wang Q, O’Connor M, Hoxie JA, Gonzalez-Scarano F (1997). CXCR-4 (fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1) is expressed in the human brain in a variety of cell types, including microglia and neurons. Am J Pathol 151: 1035–1042.PubMedGoogle Scholar
  98. Letendre SL, Lanier ER, McCutchan JA (1999). Cerebrospinal fluid beta chemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1. J Infect Dis 180: 310–319.PubMedCrossRefGoogle Scholar
  99. Lopez A, Bauer MA, Erichsen DA, Peng H, Gendelman L, Shibata A, Gendelman HE, Zheng J (2001). The regulation of neurotrophic factor activities following HIV-1 infection and immune activation of mononuclear phagocytes. Paper presented at the 31st Annual Meeting of the Society for Neuroscience, San Diego, California, November 10–15.Google Scholar
  100. Lopez-Ilasaca M (1998). Signaling from G-protein coupled receptors to mitogen activated protein (MAP) kinase cascades. Biochemical Pharmacol 56: 269–277.CrossRefGoogle Scholar
  101. Lopez-Illasaca M, Crespo P, Pellici PG, Gutkind JS, Wetzker R (1997). Linkage of G protein-coupled receptors to the MAPK signaling pathway through Pl 3-kinase γ. Science 275: 394–397.CrossRefGoogle Scholar
  102. Loy R, Taglialatela G, Angelucci L, Heyer D, Perez-Polo R (1994). Regional CNS uptake of blood-borne nerve growth factor. J Neurosci Res 39: 339–346.PubMedCrossRefGoogle Scholar
  103. Lucas AD, Chadwick N, Warren BF, Jewell DP, Gordon S, Powrie F, Greaves DR (2001). The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo. Am J Pathol 158: 855–866.PubMedGoogle Scholar
  104. Luster AD (1998). Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 338: 436–445.PubMedCrossRefGoogle Scholar
  105. Ma M, Geiger JD, Nath A (1994). Characterization of a novel binding site for the human immunodeficiency virus type 1 envelope protein gp120 on human fetal astrocytes. J Virol 68: 6824–6828.PubMedGoogle Scholar
  106. Maciejewski-Lenoir D, Chen S, Feng L, Maki R, Bacon KB (1999). Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. J Immunol 163: 1628–1635.PubMedGoogle Scholar
  107. Mackay CR (1996). Chemokine receptors and T cell chemotaxis. J Exp Med 184: 799–802.PubMedCrossRefGoogle Scholar
  108. Mallat M, Houlgatte R, Brachet P, Prochiantz A (1989). Lipopolysaccharide-stimulated rat brain macrophages release NGF in vitro. Dev Biol 133: 309–311.PubMedCrossRefGoogle Scholar
  109. Marder K, Albert S, Dooneief G, Stern Y, Ramachandran G, Epstein L (1996). Clinical confirmation of the american academy of neurology algorithm for HIV-1-associated cognitive/motor disorder. Neurology 47: 1247–1253.Google Scholar
  110. Masliah E (1996). In vivo modeling of HIV-1 mediated neurodegeneration. Am J Pathol 149: 745–750.PubMedGoogle Scholar
  111. Masliah E, DeTeresa RM, Mallory ME, Hansen LA (2000). Changes in pathological findings at autopsy in AIDS cases for the last 15 years. Aids 14: 69–74.PubMedCrossRefGoogle Scholar
  112. McArthur JC, Sacktor N, Selnes O (1999). Human immunodeficiency virus-associated dementia. Semin Neurol 19: 129–150.PubMedCrossRefGoogle Scholar
  113. McDermott DH, Halcox JP, Schenke WH, Waclawiw MA, Merrell MN, Epstein N, Quyyumi AA, Murphy PM (2001). Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis. Circ Res 89: 401–407.PubMedCrossRefGoogle Scholar
  114. 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 95: 14500–14505.PubMedCrossRefGoogle Scholar
  115. Meucci O, Fatatis A, Simen AA, Miller RJ (2000). Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci USA 97: 8075–8080.PubMedCrossRefGoogle Scholar
  116. Miller RJ, Meucci O (1999). AIDS and the brain: is there a chemokine connection? Trends Neurosci 22: 471–479.PubMedCrossRefGoogle Scholar
  117. Minami M, Satoh M (2000). Chemokines as mediators for intercellular communication in the brain (in Japanese). Nippon Yakurigaku Zasshi 115: 193–200.PubMedCrossRefGoogle Scholar
  118. Miwa T, Furukawa S, Nakajima K, Furukawa Y, Kohsaka S (1997). Lipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia. J Neurosci Res 50: 1023–1029.PubMedCrossRefGoogle Scholar
  119. Mizoue LS, Bazan JF, Johnson EC, Handel TM (1999). Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1. Biochemistry 38: 1402–1414.PubMedCrossRefGoogle Scholar
  120. Mizoue LS, Sullivan SK, King DS, Kledal TN, Schwartz TW, Bacon KB, Handel TM (2001). Molecular determinants of receptor binding and signaling by the CX3C chemokine fractalkine. J Biol Chem 276: 33906–33914.PubMedCrossRefGoogle Scholar
  121. Mollace V, Nottet HS, Clayette P, Turco MC, Muscoli C, Salvemini D, Perno CF (2001). Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants. Trends Neurosci 24: 411–416.PubMedCrossRefGoogle Scholar
  122. Moses AV, Bloom FE, Pauza CD, Nelson JA (1993). HIV infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc Natl Acad Sci USA 90: 10474–10478.PubMedCrossRefGoogle Scholar
  123. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996). Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382: 635–638.PubMedCrossRefGoogle Scholar
  124. Nath A, Geiger J (1998). Neurobiological aspects of human immunodeficiency virus infection: neurotoxic mechanisms. Prog Neurobiol 54: 19–33.PubMedCrossRefGoogle Scholar
  125. 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: 320–330.PubMedCrossRefGoogle Scholar
  126. Navia BA, Cho ES, Petito CK, Price RW (1986). The AIDS dementia complex: II. Neuropathology. Ann Neurol 19: 525–535.PubMedCrossRefGoogle Scholar
  127. Nishiyori A, Minami M, Ohtani Y, Takami S, Yamamoto J, Kawaguchi N, Kume T, Akaike A, Satoh M (1998). Localization of fractalkine and CX3CR1 mRNAs in rat brain: does fractalkine play a role in signaling from neuron to microglia? FEBS Lett 429: 167–172.PubMedCrossRefGoogle Scholar
  128. Peng H, Huang Y, Erichsen D, Zheng J (2002). HIV-1 gp120 and SDF1-α inhibit neural progenitor cell proliferation: links to HIV-1 associated dementia. Paper presented at The 32rd Annual Meeting of Society for Neuroscience, Orlando, Florida, November 2–7.Google Scholar
  129. Pereira CF, Middel J, Jansen G, Verhoef J, Nottet HS (2001). Enhanced expression of fractalkine in HIV-1 associated dementia. J Neuroimmunol 115: 168–175.PubMedCrossRefGoogle Scholar
  130. Perno CF, Crowe SM, Kornbluth RS (1997). A continuing enigma: the role of cells of macrophage lineage in the development of HIV disease. J Leukoc Biol 62: 1–3.PubMedGoogle Scholar
  131. Persidsky Y (1999). Model systems for studies of leukocyte migration across the blood-brain barrier. J NeuroVirol 5: 579–590.PubMedCrossRefGoogle Scholar
  132. Persidsky Y, Ghorpade A, Rasmussen J, Limoges J, Liu XJ, Stins M, Fiala M, Way D, Kim KS, Witte MH, et al (1999). Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis. Am J Pathol 155: 1599–1611.PubMedGoogle Scholar
  133. Pulliam L, Herndier BG, Tang NM, McGrath MS (1991). Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. J Clin Invest 87: 503–512.PubMedCrossRefGoogle Scholar
  134. Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R, Haapasalo H, Krohn K (1995). Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9: 1001–1008.PubMedCrossRefGoogle Scholar
  135. Ransohoff R (1997). Chemokines in neurological disease models: correlation between chemokine expression patterns and inflammatory pathology. J Leukoc Biol 62: 645–652.PubMedGoogle Scholar
  136. Ransohoff RM (1998). Chemokines and CNS Inflammation. Neurotransm 14: 3–12.Google Scholar
  137. Rappaport J, Joseph J, Croul S, Alexander G, Del Valle L, Amini S, Khalili K (1999). Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat. J Leukoc Biol 65: 458–465.PubMedGoogle Scholar
  138. Raychaudhuri SP, Jiang WY, Farber EM (2001). Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine. Br J Dermatol 144: 1105–1113.PubMedCrossRefGoogle Scholar
  139. Rocamora N, Pascual M, Acsady L, Lecea LD, Freund TF (1996). Expression of NGF and NT3 mRNAs hippocampal interneurons innervated by the GABAergic septo-hippocampal pathway. J Neurosci 16: 3991–4004.PubMedGoogle Scholar
  140. Ruth JH, Volin MV, Haines GK 3rd, Woodruff DC, Katschke KJ, Jr, Woods JM, Park CC, Morel JC, Koch AE (2001). Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum 44: 1568–1581.PubMedCrossRefGoogle Scholar
  141. Saad B, Constam D, Ortmann R, Moos M, Fontana A, Schachner M (1991). Astrocyte-derived TGF-β2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes. J Cell Biol 115: 473–484.PubMedCrossRefGoogle Scholar
  142. Sanders VJ, Pittman CA, White MG, Wang G, Wiley CA, Achim CL (1998). Chemokines and receptors in HIV encephalitis. AIDS 12: 1021–1026.PubMedCrossRefGoogle Scholar
  143. Schwaeble WJ, Stover CM, Schall TJ, Dairaghi DJ, Trinder PK, Linington C, Iglesias A, Schubart A, Lynch NJ, Weihe E, Schafer MK (1998). Neuronal expression of fractalkine in the presence and absence of inflammation. FEBS Lett 439: 203–207.PubMedCrossRefGoogle Scholar
  144. Sebire G, Emilie D, Wallon C, Hery C, Devergne O, Delfraissy J-F, Galanaud P, Tardieu M (1993). In vitro production of IL-6, IL-1β, and tumor necrosis factor-α by human embryonic microglial and neural cells. J Immunol 150: 1517–1523.PubMedGoogle Scholar
  145. Shieh JTC, Albright AV, Sharron M, Gartner S, Strizki J, Doms RW, Gonzalez-Scarano F (1998). Chemokine receptor utilization by human immundeficiency virus type 1 isolates that replicate in microglia. J Virol 72: 4243–4249.PubMedGoogle Scholar
  146. Strizki JM, Albright AV, Sheng H, O’Connor M, Perrin L, Gonzalez-Scarano F (1996). Infection of primary human microglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differential tropism. J Virol 70: 7654–7662.PubMedGoogle Scholar
  147. Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, et al (2000). Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. J Immunol 164: 1333–1339.PubMedGoogle Scholar
  148. 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: 6094–6100.PubMedGoogle Scholar
  149. Tsou CL, Haskell CA, Charo IF (2001). Tumor necrosis factor-alpha-converting enzyme mediates the inducible cleavage of fractalkine. J Biol Chem 276: 44622–44626.PubMedCrossRefGoogle Scholar
  150. Vallat A-V, Girolami UD, He J, Mhashikar 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.PubMedGoogle Scholar
  151. van der Meer P, Ulrich AM, Gonzalez-Scarano F, Lavi E (2000). Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia. Exp Mol Pathol 69: 192–201.PubMedCrossRefGoogle Scholar
  152. Vicenzi E, Alfano M, Ghezzi S, Gatti A, Veglia F, Lazzarin A, Sozzani S, Mantovani A, Poli G (2000). Divergent regulation of HIV-1 replication in PBMC of infected individuals by CC chemokines: suppression by RANTES, MIP-1alpha, and MCP-3, and enhancement by MCP-1. J Leukoc Biol 68: 405–412.PubMedGoogle Scholar
  153. Volin MV, Woods JM, Amin MA, Connors MA, Harlow LA, Koch AE (2001). Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol 159: 1521–1530.PubMedGoogle Scholar
  154. Wiley CA (1995). Quantitative neuropathologic assessment of HIV-1 encephalitis. Curr Top Microbiol Immunol 202: 55–61.PubMedGoogle Scholar
  155. Wiley CA, Achim C (1994). Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome. Ann Neurol 36: 673–676.PubMedCrossRefGoogle Scholar
  156. Wiley CA, Masliah E, Morey M, Lemere C, Teresa R, Grafe M, Hansen L, Terry R (1991). Neocortical damage during HIV infection. Ann Neurol 29: 651–657.PubMedCrossRefGoogle Scholar
  157. 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: 7089–7093.PubMedCrossRefGoogle Scholar
  158. Wu DT, Woodman SE, Weiss JM, McManus CM, D’Aversa TG, Hesselgesser J, Major EO, Nath A, Berman JW (2000). Mechanisms of leukocyte trafficking into the CNS. J NeuroVirol 6(Suppl 1): S82-S85.PubMedGoogle Scholar
  159. Yoshida H, Imaizumi T, Fujimoto K, Matsuo N, Kimura K, Cui X, Matsumiya T, Tanji K, Shibata T, Tamo W, et al (2001). Synergistic stimulation, by tumor necrosis factor-alpha and interferon-gamma, of fractalkine expression in human astrocytes. Neurosci Lett 303: 132–136.PubMedCrossRefGoogle Scholar
  160. Zheng J, Bauer M, Cotter RL, Ryan LA, Lopez A, Williams C, Ghorpade A, Gendelman HE (2000). Fractalkine mediated macrophage activation by neuronal injury: relevance for HIV-1 associated dementia. Paper presented at The 30th Annual Meeting of Society for Neuroscience, New Orleans, Louisiana, November 4–9.Google Scholar
  161. Zheng J, Gendelman HE (1997). The HIV-1 associated dementia complex: a metabolic encephalopathy fueled by viral replication in mononuclear phagocytes. Curr Opin Neurol 10: 319–325.PubMedCrossRefGoogle Scholar
  162. Zheng J, Lopez A, Erichsen D, Peng H, Bauer M, Williams C, Morgello S, Ghorpade A, Gendelman HE, Cotter RL, Ryan LA (2002). Neuronal fractalkine: regulation of macrophage activation and inflammatory factor production during HIV-1 associated dementia. J Immunol Submitted.Google Scholar
  163. Zheng J, Niemann D, Bauer M, Williams C, Lopez A, Erichsen D, Ryan LA, Cotter RL, Ghorpade A, Swindells S, Gendelman HE (2001). HIV-1 glia interactions in interleukin-8 and growth-related oncogene a secretion, neuronal signaling and demise: relevance for HIV-1-associated dementia. Paper presented at The 8th Conference on Retroviruses and Opportunistic Infections, Foundation for Retrovirology and Human Health, Chicago, Illinois, February 4–8.Google Scholar
  164. Zheng J, Thylin M, Ghorpade A, Xiong H, Persidsky Y, Cotter R, Niemann D, Che M, Zeng Y, Gelbard H, et al (1999). Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol 98: 185–200.PubMedCrossRefGoogle Scholar
  165. Zlotnik A, Yoshie O (2000). Chemokines: a new classification system and their role in immunity. Immunity 12: 121–127.PubMedCrossRefGoogle Scholar
  166. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR (1998). Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393: 595–599.PubMedCrossRefGoogle Scholar
  167. Zujovic V, Benavides J, Vige X, Carter C, Taupin V (2000). Fractalkine modulates TNF-alpha secretion and neurotoxicity induced by microglial activation [In Process Citation]. Glia 29: 305–315.PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2002

Authors and Affiliations

  • R. Cotter
    • 1
    • 2
  • C. Williams
    • 1
    • 2
  • L. Ryan
    • 1
    • 2
  • David Erichsen
    • 1
    • 2
  • A. Lopez
    • 1
    • 2
  • H. Peng
    • 1
    • 2
  • J. Zheng
    • 1
    • 2
    • 3
  1. 1.Laboratory of Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders985215 Nebraska Medical CenterOmahaUSA
  2. 2.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Department of PharmacologyUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations