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Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture

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Summary

To study the role of HIV-1 gp120 in loss of myelin in HIV encephalopathy, the binding of gp120 to various types of neural cells and its effects on myelination were examined in rat primary brain culture. Doublestaining of cultured cells with gp120 and specific antibodies for different neural cell types showed that gp120 bound to most of the galactocerebroside (GalC)-positive oligodendrocytes, a small population of type-2-like astrocytes and a few small neurons. Gp120 did not bind to type-1-like astrocytes, most neurons, or to macrophage/microglia. To assay myelination, cells were bathed in a myelination medium containing chick embryo extract and high glucose, with or without gp120. Seven days after the application, myelination in the culture was observed morphologically and by staining with anti-myelin basic protein (MBP) antibody, and was found to be significantly inhibited by the addition of gp120 (50–100 nM). The processes of oligodendrocytes were reduced in length and arborization relative to the control, but MBP production by oligodendrocytes was unaffected. These results show that gp120 can cause a functional disorder of oligodendrocytes and thus could underlie the diffuse loss of mylein sheaths of HIV encephalopathy.

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References

  1. Bhat S, Spitalnik SL, Gonzalez-Scarano F, Silberberg D (1991) Galactosyl ceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120. Proc Natl Acad Sci USA 88: 7131–7134

    Google Scholar 

  2. Bottenstein JE, Hunter SF (1990) Culture methods for oligodendrocyte cell lines and oligodendrocyte-type 2 astrocyte lineage cells. In: Conn PM (ed) Methods in neurosciences, vol. 2: Cell culture. Academic Press, New York, pp 56–75

    Google Scholar 

  3. Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV): a histological, immunocytochemical and electron microscopical study of 100 autopsy cases. Acta Neuropathol 75: 185–198

    Google Scholar 

  4. Budka H, Lassmann H (1988) Human immunodeficiency virus in glial cells? J Infect Dis 157: 203

    Google Scholar 

  5. Budka H (1990) Human immunodeficiency virus (HIV) envelope and core proteins in CNS tissues of patients with the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 79: 611–619

    Google Scholar 

  6. Collman R, Godfrey B, Cutilli J, Rhodes A Hassan NF, Sweet R, Douglas SD, Friedman H, Nathanson N, Gonzalez-Scarano F (1990) Macrophage-trophic strains of human immunodeficiency virus type 1 utilize the CD4 receptor. J Virol 64: 4468–4476

    Google Scholar 

  7. Cuzner ML, Davison AN, Gregson NA (1965) The chemical composition of vertebrate myelin and microsomes. J Neurochem 12: 469–481

    Google Scholar 

  8. De La Monte SM, Ho DD, Schooley RT, Hirsch MS, Richardson EP Jr (1987) Subacute encephalomyelitis of AIDS and its relation to HTLV-III infection. Neurology 37: 562–569

    Google Scholar 

  9. Dreyer EB, Kaiser PK, Offermann JT, Lipton SA (1990) HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248: 364–367

    Google Scholar 

  10. Epstein LG, Sharer LR, Cho E-S, Meyenhofer MF, Navia BA, Price RW (1985) HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res 1: 447–454

    Google Scholar 

  11. Esiri MM, Morris CS, Millard PR (1991) Fate of oligodendrocytes in HIV infection. AIDS 5: 1081–1088

    Google Scholar 

  12. Fauci AS (1988) The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239: 617–622

    Google Scholar 

  13. Gyorkey F, Melnik JL, Gyorkey P (1987) Human immunodeficiency virus in brain biopsies of patients with AIDS an progressive encephalopathy. J Infect Dis 155: 870–876

    Google Scholar 

  14. Harouse JM, Bhat S, Spitalink SL, Laughlin M, Stefano K, Silberberg DH, Gonzalez-Scarano F (1991) Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science 253: 320–323

    Google Scholar 

  15. Ichikawa M, Kimura-Kuroda J, Yasui K, Kuroda Y (1991) Expression of synaptophysin during synapse formation between dissociated cortical neurons. Neurosci Res 12: 452–458

    Google Scholar 

  16. Jordan CA, Watkins BA, Kufta C, Dubois-Dalcq M (1991) Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent. J Virol 65: 736–742

    Google Scholar 

  17. Kim SU, Sato Y, Silberberg DH, Pleasure DE, Rorke LB (1993) Long-term culture of human oligodendrocytes. J Neurol Sci 62: 295–301

    Google Scholar 

  18. Kim SU (1985) Antigen expression by glial cells grown in culture. J Neuroimmunol 8: 255–282

    Google Scholar 

  19. Kleihues P, Lang W, Burger PC, Budka H, Vogt M, Maurer R, Lüthy R, Seigenthaler W (1985) Progressive diffuse leukoencephalopathy in patients with acquired immunodeficiency syndrome (AIDS). Acta Neuropathol 68: 333–339

    Google Scholar 

  20. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Jannota 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

    Google Scholar 

  21. Kure K, Lyman WD, Weidenheim KM, Dickson DW (1990) Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immuno histochemical method. Am J Pathol 136: 1085–1092

    Google Scholar 

  22. Kuroda Y, Ichikawa M, Muramoto K, Kobayashi K, Matsuda Y, Ogura A, Kudo Y (1992) Block of synapse formation between cerebral neurons by a protein kinase inhibitor. Neurosci Lett 135: 255–258

    Google Scholar 

  23. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    Google Scholar 

  24. Lipton SA, Sucher NJ, Kaiser PK, Dreyer EB (1991) Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity. Neuron 7: 111–118

    Google Scholar 

  25. Lubetzki C, Demerens C, Anglade P, Villarroya H, Frankfurter A, Lee VM-Y, Zalc B (1993) Even in culture, oligodendrocytes myelinate solely axons. Proc Natl Acad Sci USA 90: 6820–6824

    Google Scholar 

  26. McArthur JC, Becker PS, Parisi JE, Trapp B, Selnes OA, Cornblath DR, Balakrishnan J, Griffin JW, Price D (1989) Neuropathological changes in early HIV-1 dementia. Ann Neurol 26: 681–684

    Google Scholar 

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

    Google Scholar 

  28. Merrill JE, Koyanagi Y, Zack J, Thomas L, Martin F, Chen ISY (1992) Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. J Virol 66: 2217–2225

    Google Scholar 

  29. Muramoto K, Kobayashi K, Nakanishi S, Matsuda Y, Kuroda Y (1988) Functional synapse formation between cultured neurons of rat cerebral cortex. Proc Jpn Acad Sci 64: 880–886

    Google Scholar 

  30. Navia BA, Cho E-S, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19: 525–535

    Google Scholar 

  31. Navia BA, Price RW (1987) The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. Arch Neurol 44: 65–69

    Google Scholar 

  32. Ozawa K, Saida T, Saida K, Nishitanl H, Kameyama M (1989) In vivo CNS demyelination by anti-galactocerebroside antibody. Acta Neuropathol 77: 621–628

    Google Scholar 

  33. Perry VH, Gordon S (1987) Modulation of CD4 antigen on macrophages and microglia in rat brain. J Exp Med 166: 1138–1143

    Google Scholar 

  34. Raff MC, Fields KL, Hankomori SI, Mirsky R, Pruss RM, Winter J (1979) Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res 174: 283–308

    Google Scholar 

  35. Raff MC, Miller RH, Noble M (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303: 390–396

    Google Scholar 

  36. Ranscht B, Wood PM, Bunge RP (1987) Inhibition of in vitro peripheral myelin formation by monoclonal anti-galactocerebroside. J Neurosci 7: 2936–2947

    Google Scholar 

  37. Robinson HPC, Kawahara M, Jimbo Y, Torimitsu K, Kuroda Y, Kawana A (1993) Periodic synchronized bursting and intracellular calcium transients elicited by low magnesium in cultured cortical neurons. J Neurophysiol 70: 1606–1616

    Google Scholar 

  38. Schneider-Schaulies J, Schneider-Schaulies S, Brinkmann R, Tas P, Halbrügge M, Walter U, Holmes HC, ter Meulen V (1992) HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase. Virology 191: 765–772

    Google Scholar 

  39. Schwechheimer K, Gass P, Berlet HH (1992) Expression of oligodendroglia and Schwan cell markers in human nervous system tumors. An immunohistological study and Western blot analysis. Acta Neuropathol 83: 283–291

    Google Scholar 

  40. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligoden-drocyte damage in vitro. Ann Neurol 23: 339–346

    Google Scholar 

  41. Sharer LR, Prineas JW (1988) Human immunodeficiency virus in glial cells? J Infect Dis 157: 204

    Google Scholar 

  42. Snider WD, Simpson DM, Nielsen S, Gold JWM, Metroka CE, Posner JB (1983) Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 14: 403–418

    Google Scholar 

  43. Spagnol G, Williams M, Srinivasan J, Golier J, Bauer D, Lebo RV, Latov N (1989) Molecular cloning of human myelin-associated glycoprotein. J Neurosci Res 24: 137–142

    Google Scholar 

  44. Stanhope GB, Billings-Gagliardi S, Wolf MK (1990) Myelination requirements of central nervous system glia in vitro: statistical validation of differences between glia from adult and immature mice. Glia 3: 125–129

    Google Scholar 

  45. Stoler MH, Eskin TA, Benn S, Angerer RC, Angerer LM (1986) Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. J Am Med Assoc 256: 2360–2364

    Google Scholar 

  46. Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia review. Glia 1: 301–307

    Google Scholar 

  47. Van den Berg LH, Sadiq SA, Lederman S, Latov N (1992) The gp120 glycoprotein of HIV-1 binds to sulfatide and to the myelin associated glycoprotein. J Neurosci Res 33: 513–518

    Google Scholar 

  48. Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rosenbaum W, Bureau J-F, Montagnier L, Brahic M (1987) AIDS subacute encephalitis: identification of HIV-infected cells. Am J Pathol 126: 403–410

    Google Scholar 

  49. 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

    Google Scholar 

  50. Zheng M, Fang H, Tsuruoka T, Tsuji, T, Sasaki T, Hakomori S (1993) Regulatory role of GM3 ganglioside in α5β1 integrin receptor for fibronectin-mediated adhesion of FUA169 cells. J Biol Chem 268: 2217–2222

    Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Tokyo Metropolitan Institute for Neuroscience, Tokyo

    J. Kimura-Kuroda & K. Yasui

  2. Department of Pathology, Hokkaido University, Hokkaido, Japan

    K. Nagashima

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  1. J. Kimura-Kuroda
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  2. K. Nagashima
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  3. K. Yasui
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Kimura-Kuroda, J., Nagashima, K. & Yasui, K. Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture. Archives of Virology 137, 81–99 (1994). https://doi.org/10.1007/BF01311175

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  • DOI: https://doi.org/10.1007/BF01311175

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