Skip to main content
NCBI home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;13(1):84–94. doi: 10.1111/j.1750-3639.2003.tb00009.x

Astrocyte Activation and Apoptosis: Their Roles in the Neuropathology of HIV Infection

Farideh Sabri 1, Kehmia Titanji 1, Angelo De Milito 1, Francesca Chiodi 1,✉
PMCID: PMC8095843  PMID: 12580548

Abstract

Astrogliosis is a common neuropathological finding in the brains of HIV infected individuals; both activation and apoptosis of astrocytes are seen. This review aims to discuss the Fas pathway in the context of proliferation and apoptosis of astrocytes during HIV infection, and as a result of astrogliosis, the dysregulation of astrocyte‐neuron networks. The presence of molecules reflecting astrocyte activation, which are derived from the sol‐ubilization of receptor/ligand from the surface of proliferating astrocytes, in the cerebrospinal fluid may be used to evaluate the degree of brain cell activation during HAART therapy. A better understanding of the molecular pathway(s) leading to increase activation and apoptosis of astrocytes, in parallel with studies conducted to unravel the molecules involved in T‐cell apoptosis during HIV infection, may lead to the development of new therapeutic strategies for controlling HIV replication and tissue damage.

Full Text

The Full Text of this article is available as a PDF (233.3 KB).

References

  • 1. Addo MM, Altfeld M, Rosenberg ES, Eldridge RL, Philips MN, Habeeb K, Khatri A, Brander C, Robbins GK, Mazzara GP, Goulder PJ, Walker BD; HIV Controller Study Collaboration (2001) The HIV‐1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV‐1‐infected individuals. Proc Natl Acad Sci U S A 98:1781–1786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Ambrosini E, Slepko N, Kohleisen B, Shumay E, Erfle V, Aloisi F, Levi G (1999) HIV‐1 Nef alters the expression of beta II and epsilon isoforms of protein kinase C and the activation of the long terminal repeat promoter in human astrocytoma cells. GLIA 27:143–151. [PubMed] [Google Scholar]
  • 3. Aquaro S, Panti S, Caroleo MC, Balestra E, Cenci A, Forbici F, Ippolito G, Mastino A, Testi R, Mollace V, Calio R, Perno CF (2000) Primary macrophages infected by human immunodeficiency virus trigger CD95‐mediated apoptosis of uninfected astrocytes. J Leukoc Biol 68:429–435. [PubMed] [Google Scholar]
  • 4. Aukrust P, Muller F, Lien E (1999) Tumor necrosis factor (TNF) system levels in human immunodeficiency virus‐infected patients during highly active antiretroviral therapy: persistent TNF activation is associated with virologic and immunologic treatment failure. J Infect Dis 179:74–82. [DOI] [PubMed] [Google Scholar]
  • 5. Badley AD, Parato K, Cameron DW (1999) Dynamic correlation of apoptosis and immune activation during treatment of HIV infection. Cell Death Differ 6:420–432. [DOI] [PubMed] [Google Scholar]
  • 6. Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R, Pomerantz RJ (1996) Cellular reservoirs of HIV‐1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10:573–585. [DOI] [PubMed] [Google Scholar]
  • 7. Bajetto A, Barbero S, Bonavia R, Piccioli P, Pirani P, Florio T, Schettini G (2001) Stromal cell‐derived factor‐1α induces astrocyte proliferation through the activation of extracellular signal‐regulated kinases ½ pathway. J Neurochem 77:1226–1236. [DOI] [PubMed] [Google Scholar]
  • 8. Bartz SR and Emerman M (1999): Human immunodeficiency virus type 1 tat induces apoptosis and increases sensitivity to apoptotic signals by up‐regulating FLICE/Caspase‐8. J Virol 73:1956–1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Becher B, D'Souza SD, Troutt AB, Antel JP (1998) Fas expression on human fetal astrocytes without susceptibility to Fas‐mediated cytotoxicity. Neuroscience 84:627–634. [DOI] [PubMed] [Google Scholar]
  • 10. Bechmann I, Mor G, Nilsen J, Eliza M, Nitxch R, Naftolin F (1999) FasL (CD95L, Apo1 L) is expressed in the normal rat and human brain:Evidence for the existence of an immunological brain barrier. GLIA 27:62–74. [DOI] [PubMed] [Google Scholar]
  • 11. Bechmann I, Lossau S, Steiner B, Mor G, Gimsa U, Nitsch R (2000) Reactive astrocytes upregulate Fas (CD95) and Fas Ligand (CD95L) expression but do not undergo programmed cell death during the course of anterograde degeneration. GLIA 32:25–41. [DOI] [PubMed] [Google Scholar]
  • 12. Beer R, Franz G, Srinivasan A, Hayes RL, Pike BR, New‐comb JK, Zhao X, Schmutzhard E, Poewe W, Kampfl A (2000) Temporal profile and cell subtype distribution of activated caspase‐3 following experimental traumatic brain injury. J Neurochem 75:1264–1273. [DOI] [PubMed] [Google Scholar]
  • 13. Bezzi P (1998) Prostaglandins stimulate calcium‐dependent glutamate release in astrocytes. Nature 391:281–285. [DOI] [PubMed] [Google Scholar]
  • 14. Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vexcovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4‐activated astrocyte glutamate release via TNFα:amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710. [DOI] [PubMed] [Google Scholar]
  • 15. Brack‐Werner R, Kleinschmidt A, Ludvigsen A, Mellert W, Neumann M, Herrmann R, Khim MC, Burny A, Muller‐Lantzsch N, Stavrou D et al (1992) Infection of human brain cells by HIV‐1: restricted virus production in chronically infected human glial cell lines. AIDS 6:273–285. [PubMed] [Google Scholar]
  • 16. Cascino I, Fiucci G, Papoff G, Ruberti G (1995) Three functional soluble forms of the human apoptosis‐inducing Fas molecule are produced by alternative splicing. J Immunol 154:2706–2713. [PubMed] [Google Scholar]
  • 17. Chang L, Ernst T, Leonido‐Yee M, Witt M, Speck O, Walot I, Miller EN (1999) Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53:782–789. [DOI] [PubMed] [Google Scholar]
  • 18. Chiodi F, Fuerstenberg S, Gidlund M, Asjo B, Fenyo EM (1987) Infection of brain‐derived cells with the human immunodeficiency virus. J Virol 61:1244–1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Choi C, Park JY, Lee J, Lim JH, Shin EC, Ahn YS, Kim CH, Kim SJ, Kim JD, Choi IS, Choi IH (1999) Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL‐1, IL‐6, TNF‐alpha, or IFN‐gamma. J Immunol 162:1889–1895. [PubMed] [Google Scholar]
  • 20. Choppin J, Cohen W, Bianco A, Briand JP, Connan F, Dalod M, Guillet JG (2001) Characteristics of HIV‐1 Nef regions containing multiple CD8+ T‐cell epitopes: wealth of HLA‐binding motifs and sensitivity to proteasome degradation. J Immunol 166:6164–6169. [DOI] [PubMed] [Google Scholar]
  • 21. Colamussi ML, Secchiero P, Gonelli A, Marchisio M, Zauli G, Capitani S (2001) Stromal derived factor‐1 alpha (SDF‐1 alpha) induces CD4+ T‐cell apoptosis via the functional up‐regulation of the Fas (CD95)/Fas ligand (CD95L) pathway. J Leukoc Biol 69:263–70. [PubMed] [Google Scholar]
  • 22. Da Cunha A, Jefferson JJ, Tyor WR, Glass JD, Hannotta FS, Vitkov L (1993) Gliosis in human brain: relationship to size but not to other properties of astrocytes. Brain Res 600:161–166. [DOI] [PubMed] [Google Scholar]
  • 23. D'Arminio Monforte A, Duca PG, Vago L, Grassi MP, Moroni M (2000) Decreasing incidence of CNS AIDS‐defining events associated with antiretroviral therapy. Neurology 54:1856–1859. [DOI] [PubMed] [Google Scholar]
  • 24. De Milito A, Hejdeman B, Albert J, Aleman S, Sonnerborg A, Zazzi M, Chiodi F (2000) High plasma levels of soluble fas in HIV type 1‐infected subjects are not normalized during highly active antiretroviral therapy. AIDS Res Hum Retroviruses 16:1379–1384. [DOI] [PubMed] [Google Scholar]
  • 25. De Milito A, Aleman S, Marenzi R, Sönnerborg S, Fuchs D, Zazzi M, Chiodi F (2002) Plasma levels of soluble CD27: a simple marker to monitor immune activation during potent antiretroviral therapy in HIV‐1‐infected subjects. Clin Exp Immunol 127:486–494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. De Oliveira Pinto LM, Garcia S, Lecoeur H, Rapp C, Patey O, Goeugeon ML (2002) Increased sensitivity of T lymphocytes to tumor necrosis factor receptor 1 (TNFR1)‐ and TNFR2‐mediated apoptosis in HIV infection: relation to expression of Bcl‐2 and active caspase‐8 and caspase‐3. Blood 99:1666–1675. [DOI] [PubMed] [Google Scholar]
  • 27. De Oliveira, Pinto LM , Lecoeur H, Ledru E, Rapp C, Patey O, Goeugeon, ML (2002) Lack of control of T‐cell apoptosis under HAART. Influence of therapy regimen in vivo and in vitro. AIDS 16:329–339. [DOI] [PubMed] [Google Scholar]
  • 28. Dorf ME, Berman MA, Tanabe S, Heesen M, Luo Y (2000) Astrocytes express functional chemokine receptors. J Neuroimmunol 111:109–121. [DOI] [PubMed] [Google Scholar]
  • 29. Dyrhol‐Riise AM, Stent G, Rosok BI, Voltersvik P, Olofsson J, Asjo B (2001) The Fas/FasL system and T‐cell apoptosis in HIV‐1‐infected lymphoid tissue during highly active antiretroviral therapy. Clin Immunol 101:169–179. [DOI] [PubMed] [Google Scholar]
  • 30. Elovaara I, Sabri F, Gray F, Alafuzoff I, Chiodi F (1999) Upregulated expression of Fas and Fas ligand in brain through the spectrum of HIV‐1 infection. Acta Neuropathol (Berl) 98:355–362. [DOI] [PubMed] [Google Scholar]
  • 31. Epstein LG, Sharer LR, Cho ES, Myenhofer M, Navia B, Price RW (198485) HTLV‐III/LAV‐like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res 1:447–454. [DOI] [PubMed] [Google Scholar]
  • 32. Garden GA, Budd SL, Tsai E, Hanson L, Kaul M, D'Emilia DM, Friedlander RM, Yuan J, Masliah E, Lipton SA (2002) Caspase cascades in human immunodeficiency virus‐associated neurodegeneration. J Neurosci 22:4015–4024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Geleziunas, Xu W , Takeda K, Ichijo H, Greene WC (2001) HIV‐1 Nef inhibits ASK1‐dependent death signaling providing a potential mechanism for protecting the infected host cell. Nature 410:834–838. [DOI] [PubMed] [Google Scholar]
  • 34. Gougeon ML, Laurent‐Crawford AG Hovanessian AG, Montagnier L (1993) Direct and indirect mechanisms mediating apoptosis during HIV infection: contribution to in vivo CD4 T‐cell depletion. Semin Immunol 5:187–194. [DOI] [PubMed] [Google Scholar]
  • 35. Gougeon ML and Montagnier L (1999) Programmed cell death as a mechanism of CD4 and CD8 T‐cell deletion in AIDS. Molecular control and effect of highly active anti‐retroviral therapy. Ann N Y Acad Sci 887:199–212. [DOI] [PubMed] [Google Scholar]
  • 36. Gray F, Adle‐Biassette H, Brion F, Ereau T, le Maner I, Levy V, Corcket G (2000) Neuronal apoptosis in human immunodeficiency virus infection. J Neurovirol 6:S38–43. [PubMed] [Google Scholar]
  • 37. Gupta S (2001) Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci 69:2957–2964. [DOI] [PubMed] [Google Scholar]
  • 38. Hansson E, Ronnback L (1995) Astrocytes in glutamate neurotransmission. FASEB J 9:343–350. [DOI] [PubMed] [Google Scholar]
  • 39. Hesselgesser J, Halks‐Miller M, DelVecchio V, Peiper SC, Hoxie J, Kolson DL, Taub D, Horuk R (1997) CD4‐independent association between HIV‐1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons. Curr Biol 7: 112–121. [DOI] [PubMed] [Google Scholar]
  • 40. Hornig M, Weissenbock H, Horscroft N, Lipkin WI (1999): An infection‐based model of neurodevelopmental damage. Proc Natl Acad Sci 96:12102–12107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Horuk R, Martin AW, Wang Z, Schweitzer L, Gerassimides A, Guo H, Lu Z, Hesselgesser J, Perez HD, Kim J, Parker J, Hadley TJ, Peiper SC (1997) Expression of chemokine receptors by subsets of neurons in the central nervous system. J Immunol 158:2882–2890. [PubMed] [Google Scholar]
  • 42. Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66:233–243. [DOI] [PubMed] [Google Scholar]
  • 43. Ju ST, Panka DJ, Cui H, Ettinger R, El‐Khatib M, Sherr DH, Stanger BZ and Marshak‐Rothstein A: Fas (CD95)/Fas L interactions required for programmed cell death after T‐cell activation. Nature 373:444–448. [DOI] [PubMed] [Google Scholar]
  • 44. Keys B, Albert J, Kovamees J, Chiodi F (1987) Infection of brain‐derived cells with the human immunodeficiency virus. J Virol 61:1244–1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, 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. [DOI] [PubMed] [Google Scholar]
  • 46. Kohleisen B, Shumay E, Sutter G, Foerster R, Brack‐Werner R, Nuesse M, Erfle V (1999) Stable expression of HIV‐1 Nef induces changes in growth properties and activation state of human astrocytes. AIDS 13:2331–2341. [DOI] [PubMed] [Google Scholar]
  • 47. Krams SM, Fox CK, Beatty PR, Cao S, Villanueva JC, Esquivel CO, Martinez OM (1998) Human hepatocytes produce an isoform of FAS that inhibits apoptosis. Transplantation 65:713–721. [DOI] [PubMed] [Google Scholar]
  • 48. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Langford D, Sanders VJ, Mallory M, Kaul M, Masliah E (2002) Expression of stromal cell‐derived factor 1 alpha protein in HIV encephalitis. J Neuroimmunol 127:115–126. [DOI] [PubMed] [Google Scholar]
  • 50. Marcondes MC, Burudi EM, Huitron‐Resendiz S, Sanchez‐Alavez M, Watry D, Zandonatti M, Henriksen SJ, Fox HS (2001). Highly activated CD8 (+) T‐cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. J Immunol 167:5429–5438. [DOI] [PubMed] [Google Scholar]
  • 51. Martinez M, Fernandez‐Vivancos E, Frank A, De la Fuente M, Hernanz A (2000) Increased cerebrospinal fluid fas (Apo‐1) levels in Alzheimer's disease. Relationship with IL‐6 concentrations. Brain Res 869:216–219. [DOI] [PubMed] [Google Scholar]
  • 52. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53. Meyaard L, Otto SA, Jonker RR, Mijnster MJ, Keet RP, Miedema F (1992) Programmed death of T‐cells in HIV‐1 infection. Science 257:217–219. [DOI] [PubMed] [Google Scholar]
  • 54. Neumann M, Felber BK, Kleinschmidt A, Froese B, Erfle V, Pavlakis GN, Brack‐Werner R (1995) Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. J Virol 69:2159–2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Novitsky V, Rybak N, McLane MF, Gilbert P, Chigwedere P, Klein I, Gaolekwe S, Chang SY, Peter T, Thior I, Ndung'u T, Vannberg F, Foley BT, Marlink R, Lee TH, Essex M (2001) Identification of human immunodeficiency virus type 1 subtype C Gag‐, Tat‐, Rev‐, and Nef‐specific elispot‐based cytotoxic T‐lymphocyte responses for AIDS vaccine design. J Virol 75:9210–9228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Ohagen A, Glosh 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Ohtani Y, Minami M, Kawaguchi N, Nishiyori A, Yamamoto J, Takami S, Satoh M (1998) Expression of stromal cell‐derived factor‐1 and CXCR4 chemokine receptor mRNAs in cultured rat glial and neuronal cells. Neurosci Lett 249:163–166. [DOI] [PubMed] [Google Scholar]
  • 58. Palma JP, Yauch RL, Lang S, Kim BS (1999): Potential role of CD4+ T‐cell‐mediated apoptosis of activated astrocytes in Theiler's virus‐induced demyelination. J Immunol 162:6543–6551. [PubMed] [Google Scholar]
  • 59. Parlato S, Santini SM, Lapenta C, Spada M, Logozzi M, Rizza P, Proietti E, Belardelli F, Fais S (2000) Primary HIV‐1 infection of human CD4+ T‐cells passaged into SCID mice leads to selection of chronically infected cells through a massive fas‐mediated autocrine suicide of uninfected cells. Cell Death Differ 7:37–47. [DOI] [PubMed] [Google Scholar]
  • 60. Parpura V (1994) Glutamate‐mediated astrocyte‐neuron signalling. Nature 369:744–747. [DOI] [PubMed] [Google Scholar]
  • 61. Plana M, Garcia F, Gallart T (2000) Immunological benefits of antiretroviral therapy in very early stages of asymptomatic chronic HIV‐1 infection. AIDS 14:1921–1933. [DOI] [PubMed] [Google Scholar]
  • 62. Rasola A, Gramaglia D, Boccaccio C, Comoglio PM (2001) Apoptosis enhancement by the HIV‐1 Nef protein. J Immunol 166:81–88. [DOI] [PubMed] [Google Scholar]
  • 63. Richard A, Robichaud G, Lapointe R, Bourgoin S, Darveau A, Poulin L (1997) Interference of HIV‐1 Nef in the sphingomyelin transduction pathway activated by tumour necrosis factor‐alpha in human glial cells. AIDS 11:F1–7. [DOI] [PubMed] [Google Scholar]
  • 64. Roggero R, Robert‐Hebman V, Harrington S, Roland J, Vergne L, Jaleco S, Devaux C, Biard‐Piechaczyk M (2001) Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c‐mediated apoptosis independently of Fas signalling. J Virol 75:7637–7650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65. Saas P, Boucraut J, Quiquerez A‐L, Schnuriger V, Perrin G, Desplat‐Jego S, Bernard D, Walker PR, Dietrich P‐Y (1999) CD95 (Fas/Apo‐1) as a receptor governing astrocyte apoptotic or inflammatory responses: A key role in bran inflammation J Immunol 162:2326–2333. [PubMed] [Google Scholar]
  • 66. 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. [DOI] [PubMed] [Google Scholar]
  • 67. Sabri F, De Milito A, Pirskanen R, Elovaara I, Hagberg L, Cinque P, Price R, Chiodi F (2001) Elevated levels of soluble Fas and Fas ligand in cerebrospinal fluid of patients with AIDS dementia complex. J Neuroimmunol 114:197–206. [DOI] [PubMed] [Google Scholar]
  • 68. Sacktor NC, Skolasky RL, Lyles RH, Esposito D, Selnes OA, McArthur JC (2000) Improvement in HIV‐associated motor slowing after antiretroviral therapy including protease inhibitors. J Neurovirol 6:84–88. [DOI] [PubMed] [Google Scholar]
  • 69. 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 44:474–481. [DOI] [PubMed] [Google Scholar]
  • 70. Schneider P, Holler N, Bodmer J‐L, Hahne M, Frei K, Fontana A, Tschopp J, (1998) Conversion of membrane‐bound Fas (CD95) ligand to its soluble form is associated with down‐regulation of its proapoptotic activity and loss of liver toxicity. J Exp Med 187:1205–1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71. Schweighardt B, Shieh JT, Atwood WJ (2001) CD4/CXCR4‐independent infection of human astrocytes by a T‐tropic strain of HIV‐1. J Neurovirol 7:155–162. [DOI] [PubMed] [Google Scholar]
  • 72. Screaton G and Xu XN (2000) T‐cell life and death signaling via TNF‐receptor family members. Curr Opin Immunol 12:316–322. [DOI] [PubMed] [Google Scholar]
  • 73. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74. Sloand EM, Kumar PN, Kim S, Chaudhuri A, Weichold FF, Young NS (1999) Human immunodeficiency virus type 1 protease inhibitor modulates activation of peripheral blood CD4(+) T‐cells and decreases their susceptibility to apoptosis in vitro and in vivo. Blood 94:1021–1027. [PubMed] [Google Scholar]
  • 75. Suda T, Hashimoto H, Tanaka M, Ochi T and Nagata S (1997) Membrane Fas ligand kills human peripheral blood T lymphocytes and soluble Fas ligand blocks the killing. J Exp Med 186:2045–2050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Thilenius ARB, Sabelko‐Downes KA, Russell JH (1999) The role of the antigen‐presenting cell in Fas‐mediated direct and bystander killing: potential in vivo function of Fas in Experimental Allergic Encephalomyelitis. J Immunol 162:643–650. [PubMed] [Google Scholar]
  • 77. Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316. [DOI] [PubMed] [Google Scholar]
  • 78. 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. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79. Tornatore C, Chandra R, Berger JR, Major EO (1994) HIV‐1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44:481–487. [DOI] [PubMed] [Google Scholar]
  • 80. Vigano A, Saresella M, Rusconi S, Ferrante P, Clerici M (1998) Expression of CD38 on CD8 T‐cells predicts maintenance of high viraemia in HAART‐treated HIV‐1‐infected children. Highly active antiretroviral therapy. Lancet 352:1905–1906. [DOI] [PubMed] [Google Scholar]
  • 81. Vlahakis SR, Algeciras‐Schimnich A, Bou G, Heppelmann CJ, Villasis‐Keever A, Collman RG, Paya CV (2001): Chemokine‐receptor activation by env determines the mechanism of death in HIV‐infected and uninfected T lymphocytes. J Clin Invest 107:207–215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB (1986) Cellular localisation of human immunodeficiency virus infection within the brains of acquired immunodeficiency syndrome patients. Proc Natl Acad Sci U S A 83:7089–7093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83. Wiley CA, Masliah E, Morey M, Lemere C, DeTeresa R, Grafe M, Hansen L, Terry R (1991) Neocortical damage during HIV infection. Ann Neurol 29:651–657. [DOI] [PubMed] [Google Scholar]
  • 84. Wosik K, Becher B, Ezman A, Nalbantoglu J, Antel J (2001) Caspase 8 expression and Signaling in Fas Injury‐Resistant Human Fetal Astrocytes. GLIA 33:217–224. [DOI] [PubMed] [Google Scholar]
  • 85. Xu X‐N, Laffert B, Screaton GR, Kraft M, Wolf D, Kolanus W, Mongkolsapay J, McMichael AJ, Baur AS (1999) Induction of Fas ligand expression by HIV involves the interaction of Nef with the T‐cell receptor ζ chain. J Exp Med 189:1489–1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86. 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. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES