Childs, E. A. et al. Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology52, 607–613 (1999). ArticleCASPubMed Google Scholar
McArthur, J. C. et al. Human immunodeficiency virus-associated dementia: an evolving disease. J. Neurovirol.9, 205–221 (2003). Excellent review of the changing patterns of neurological manifestations of AIDS in the era of HAART, including comments about neuropathy. ArticleCASPubMed Google Scholar
Cherner, M. et al. Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology59, 1563–1567 (2002). Describes the importance of MCMD in the spectrum of neuropathogenesis of AIDS. ArticleCASPubMed Google Scholar
Sacktor, N. et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J. Neurovirol.8, 136–142 (2002). ArticleCASPubMed Google Scholar
Neuenburg, J. K. et al. HIV-related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr.31, 171–177 (2002). ArticlePubMed Google Scholar
Letendre, S. L, et al. Enhancing antiretroviral therapy for HIV cognitive disorders. Ann. Neurol.56, 416–423 (2004). ArticlePubMed Google Scholar
Clements, J. E. & Zink, M. C. Molecular biology and pathogenesis of animal lentivirus infections. Clin. Microbiol. Rev.9, 100–117 (1996). Excellent review of the spectrum of diseases caused by lentiviruses. Also provides a historical perspective not present in more recent reviews. ArticleCASPubMedPubMed Central Google Scholar
An, S. F., Groves, M., Gray, F. & Scaravilli, F. Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. J. Neuropathol. Exp. Neurol.58, 1156–1162 (1999). ArticleCASPubMed Google Scholar
Davis, L. E. et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology42, 1736–1739 (1992). ArticleCASPubMed Google Scholar
Hickey, W. F. Leukocyte traffic in the central nervous system: the participants and their roles. Semin. Immunol.11, 125–137 (1999). ArticleCASPubMed Google Scholar
Peluso, R., Haase, A., Stowring, L., Edwards, M. & Ventura, P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology147, 231–236 (1985). ArticleCASPubMed Google Scholar
Wiley, C. A., Schrier, R. D., Nelson, J. A., Lampert, P. W. & Oldstone, M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc. Natl Acad. Sci. USA83, 7089–7093 (1986). Reference 13, together with references 15–17, provides the currently accepted evidence for infection of CNS cells. These references emphasize the role of perivascular macrophages, and reference 16 also provides an alternative point of view regarding the involvement of microglia. ArticleCASPubMed Google Scholar
Takahashi, K. et al. Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann. Neurol.39, 705–711 (1996). ArticleCASPubMed Google Scholar
Fischer-Smith, T. et al. Macrophage/microglial accumulation and proliferating cell nuclear antigen expression in the central nervous system in human immunodeficiency virus encephalopathy. Am. J. Pathol.164, 2089–2099 (2004). ArticleCASPubMedPubMed Central Google Scholar
Cosenza, M. A., Zhao, M. L., Si, Q. & Lee, S. C. Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol.12, 442–455 (2002). ArticleCASPubMed Google Scholar
Williams, K. C. et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J. Exp. Med.193, 905–915 (2001). ArticleCASPubMedPubMed Central Google Scholar
Pumarola-Sune, T., Navia, B. A., Cordon-Cardo, C., Cho, E. S. & Price, R. W. HIV antigen in the brains of patients with the AIDS dementia complex. Ann. Neurol.21, 490–496 (1987). ArticleCASPubMed Google Scholar
Petito, C. K. & Cash, K. S. Blood–brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann. Neurol.32, 658–666 (1992). ArticleCASPubMed Google Scholar
Williams, K. C. & Hickey, W. F. Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu. Rev. Neurosci.25, 537–562 (2002). ArticleCASPubMed Google Scholar
Gartner, S. HIV infection and dementia. Science287, 602–604 (2000). References 20 and 21 are good reviews that discuss the contribution of infection and cellular activation to neuropathogenesis caused by HIV. ArticleCASPubMed Google Scholar
Bomsel, M. Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nature Med.3, 42–47 (1997). ArticleCASPubMed Google Scholar
Banks, W. A. et al. Transport of human immunodeficiency virus type 1 pseudoviruses across the blood–brain barrier: role of envelope proteins and adsorptive endocytosis. J. Virol.75, 4681–4691 (2001). ArticleCASPubMedPubMed Central Google Scholar
Liu, N. Q. et al. Human immunodeficiency virus type 1 enters brain microvascular endothelia by macropinocytosis dependent on lipid rafts and the mitogen-activated protein kinase signaling pathway. J. Virol.76, 6689–6700 (2002). ArticleCASPubMedPubMed Central Google Scholar
Argyris, E. G. et al. Human immunodeficiency virus type 1 enters primary human brain microvascular endothelial cells by a mechanism involving cell surface proteoglycans independent of lipid rafts. J. Virol.77, 12140–12151 (2003). ArticleCASPubMedPubMed Central Google Scholar
Bobardt, M. D. et al. Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J. Virol.78, 6567–6584 (2004). ArticleCASPubMedPubMed Central Google Scholar
Edinger, A. L. et al. CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc. Natl Acad. Sci. USA94, 14742–14747 (1997). ArticleCASPubMed Google Scholar
Gehrmann, J., Matsumoto, Y. & Kreutzberg, G. W. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Brain Res. Rev.20, 269–287 (1995). ArticleCASPubMed Google Scholar
Carson, M. J., Reilly, C. R., Sutcliffe, J. G. & Lo, D. Mature microglia resemble immature antigen-presenting cells. Glia22, 72–85 (1998). ArticleCASPubMed Google Scholar
Shaked, I., Porat, Z., Gersner, R., Kipnis, J. & Schwartz, M. Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J. Neuroimmunol.146, 84–93 (2004). ArticleCASPubMed Google Scholar
Kipnis, J., Avidan, H., Caspi, R. R. & Schwartz, M. Dual effect of CD4+CD25+ regulatory T cells in neurodegeneration: a dialogue with microglia. Proc. Natl Acad. Sci. USA101 (Suppl. 2), 14663–14669 (2004). ArticleCASPubMed Google Scholar
Del Rio-Hortega, P. in Cytology and Cellular Pathology of the Nervous System (ed. Penfield, W.) 483–534 (Hoeber, New York, 1932). Google Scholar
Guillemin, G. J. & Brew, B. J. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J. Leukoc. Biol.75, 388–397 (2004). ArticleCASPubMed Google Scholar
Ulvestad, E. et al. Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. J. Leukoc. Biol.56, 732–740 (1994). ArticleCASPubMed Google Scholar
Ulvestad, E., Williams, K., Mork, S., Antel, J. & Nyland, H. Phenotypic differences between human monocytes/macrophages and microglial cells studied in situ and in vitro. J. Neuropathol. Exp. Neurol.53, 492–501 (1994). ArticleCASPubMed Google Scholar
Lassmann, H., Schmied, M., Vass, K. & Hickey, W. F. Bone marrow derived elements and resident microglia in brain inflammation. Glia7, 19–24 (1993). ArticleCASPubMed Google Scholar
Hickey, W. F., Vass, K. & Lassmann, H. Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J. Neuropathol. Exp. Neurol.51, 246–256 (1992). ArticleCASPubMed Google Scholar
Krall, W. J., Challita, P. M., Perlmutter, L. S., Skelton, D. C. & Kohn, D. B. Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation. Blood83, 2737–2748 (1994). CASPubMed Google Scholar
Unger, E. R. et al. Male donor-derived cells in the brains of female sex-mismatched bone marrow transplant recipients: a Y-chromosome specific in situ hybridization study. J. Neuropathol. Exp. Neurol.52, 460–470 (1993). ArticleCASPubMed Google Scholar
Fischer-Smith, T. et al. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J. Neurovirol.7, 528–541 (2001). Shows that the CD14+CD16+ monocyte subpopulation accumulates in the CNS and potentially has a role in HAD. ArticleCASPubMed Google Scholar
Shieh, J. T. et al. Chemokine receptor utilization by human immunodeficiency virus type 1 isolates that replicate in microglia. J. Virol.72, 4243–4249 (1998). CASPubMedPubMed Central Google Scholar
Strizki, J. M. et al. 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 (1996). CASPubMedPubMed Central Google Scholar
Watkins, B. A. et al. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science249, 549–553 (1990). ArticleCASPubMed Google Scholar
Rottman, J. B. et al. Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am. J. Pathol.151, 1341–1351 (1997). CASPubMedPubMed Central Google Scholar
Albright, A. V. et al. 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 (1999). CASPubMedPubMed Central Google Scholar
van der Meer, P., Ulrich, A. M., González-Scarano, F. & Lavi, E. Immunohistochemical analysis of CCR2, CCR3, CCR5, and CXCR4 in the human brain: potential mechanisms for HIV dementia. Exp. Mol. Pathol.69, 192–201 (2000). ArticleCASPubMed Google Scholar
Sharer, L. R. et al. Pathologic features of AIDS encephalopathy in children: evidence for LAV/HTLV-III infection of brain. Hum. Pathol.17, 271–284 (1986). ArticleCASPubMed Google Scholar
Sharer, L. R., Cho, E. S. & Epstein, L. G. Multinucleated giant cells and HTLV-III in AIDS encephalopathy. Hum. Pathol.16, 760 (1985). ArticleCASPubMed Google Scholar
Dick, A. D., Pell, M., Brew, B. J., Foulcher, E. & Sedgwick, J. D. Direct ex vivo flow cytometric analysis of human microglial cell CD4 expression: examination of central nervous system biopsy specimens from HIV-seropositive patients and patients with other neurological disease. AIDS11, 1699–1708 (1997). ArticleCASPubMed Google Scholar
Peudenier, S., Hery, C., Montagnier, L. & Tardieu, M. Human microglial cells: characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV-1 infection. Ann. Neurol.29, 152–161 (1991). ArticleCASPubMed Google Scholar
Peudenier, S., Hery, C., Ng, K. H. & Tardieu, M. HIV receptors within the brain: a study of CD4 and MHC-II on human neurons, astrocytes and microglial cells. Res. Virol.142, 145–149 (1991). ArticleCASPubMed Google Scholar
Jordan, C. A., Watkins, B. A., Kufta, C. & Dubois-Dalcq, M. Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent. J. Virol.65, 736–742 (1991). CASPubMedPubMed Central Google Scholar
Hickey, W. F., Hsu, B. L. & Kimura, H. T-lymphocyte entry into the central nervous system. J. Neurosci. Res.28, 254–260 (1991). ArticleCASPubMed Google Scholar
Shapshak, P. et al. Independent evolution of HIV type 1 in different brain regions. AIDS Res. Hum. Retroviruses15, 811–820 (1999). ArticleCASPubMed Google Scholar
Epstein, L. G. et al. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology180, 583–590 (1991). ArticleCASPubMed Google Scholar
Kodama, T., Mori, K., Kawahara, T., Ringler, D. J. & Desrosiers, R. C. Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS. J. Virol.67, 6522–6534 (1993). CASPubMedPubMed Central Google Scholar
Korber, B. T. et al. Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J. Virol.68, 7467–7481 (1994). CASPubMedPubMed Central Google Scholar
Reddy, R. T. et al. Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis. AIDS Res. Hum. Retroviruses12, 477–482 (1996). ArticleCASPubMed Google Scholar
Wong, J. K. et al. In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues. J. Virol.71, 2059–2071 (1997). CASPubMedPubMed Central Google Scholar
Ryzhova, E. V. et al. Simian immunodeficiency virus encephalitis: analysis of envelope sequences from individual brain multinucleated giant cells and tissue samples. Virology297, 57–67 (2002). ArticleCASPubMed Google Scholar
Miyake, A. et al. The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages. Arch. Virol.149, 943–955 (2004). ArticleCASPubMed Google Scholar
Gorry, P. R. et al. Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate. J. Virol.76, 6277–6292 (2002). Indicates that increased neurovirulence might be associated with a higher efficiency in the interaction of the HIV envelope and the viral co-receptor CCR5. ArticleCASPubMedPubMed Central Google Scholar
Martín, J., LaBranche, C. C. & González-Scarano, F. Differential CD4/CCR5 utilization, gp120 conformation, and neutralization sensitivity between envelopes from a microglia-adapted human immunodeficiency virus type 1 and its parental isolate. J. Virol.75, 3568–3580 (2001). ArticlePubMedPubMed Central Google Scholar
Watry, D., Lane, T. E., Streb, M. & Fox, H. S. Transfer of neuropathogenic simian immunodeficiency virus with naturally infected microglia. Am. J. Pathol.146, 914–923 (1995). CASPubMedPubMed Central Google Scholar
Peters, P. J. et al. Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages. J. Virol.78, 6915–6926 (2004). First study that shows a reduced CD4 dependence of viral envelopes from primary brain-derived HIV isolates compared with peripheral isolates, in HIV-infected individuals. ArticleCASPubMedPubMed Central Google Scholar
Martín-García, J., Kolson, D. L. & González-Scarano, F. Chemokine receptors in the brain: their role in HIV infection and pathogenesis. AIDS16, 1709–1730 (2002). ArticlePubMed Google Scholar
Horuk, R. et al. Expression of chemokine receptors by subsets of neurons in the central nervous system. J. Immunol.158, 2882–2890 (1997). CASPubMed Google Scholar
Coughlan, C. M. et al. Expression of multiple functional chemokine receptors and monocyte chemoattractant protein-1 in human neurons. Neuroscience97, 591–600 (2000). ArticleCASPubMed Google Scholar
Meucci, O. et al. Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc. Natl Acad. Sci. USA95, 14500–14505 (1998). Indicates a role for certain chemokine–chemokine receptor interactions in neuroprotection, in addition to their proposed role in neurotoxicity. ArticleCASPubMed Google Scholar
Xia, M. Q., Bacskai, B. J., Knowles, R. B., Qin, S. X. & Hyman, B. T. Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer's disease. J. Neuroimmunol.108, 227–235 (2000). ArticleCASPubMed Google Scholar
Tanabe, S. et al. Functional expression of the CXC-chemokine receptor-4/fusin on mouse microglial cells and astrocytes. J. Immunol.159, 905–911 (1997). CASPubMed Google Scholar
Bajetto, A. et al. Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1. J. Neurochem.73, 2348–2357 (1999). ArticleCASPubMed Google Scholar
Lavi, E., Kolson, D. L., Ulrich, A. M., Fu, L. & González-Scarano, F. Chemokine receptors in the human brain and their relationship to HIV infection. J. Neurovirol.4, 301–311 (1998). Reviews the expression of chemokine receptors in the brain and their relevance to neuropathogenesis caused by HIV. ArticleCASPubMed Google Scholar
Dorf, M. E., Berman, M. A., Tanabe, S., Heesen, M. & Luo, Y. Astrocytes express functional chemokine receptors. J. Neuroimmunol.111, 109–121 (2000). ArticleCASPubMed Google Scholar
Westmoreland, S. V., Rottman, J. B., Williams, K. C., Lackner, A. A. & Sasseville, V. G. Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis. Am. J. Pathol.152, 659–665 (1998). CASPubMedPubMed Central Google Scholar
Vallat, A. V. et al. Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS. Am. J. Pathol.152, 167–178 (1998). CASPubMedPubMed Central Google Scholar
Xia, M. Q., Qin, S. X., Wu, L. J., Mackay, C. R. & Hyman, B. T. Immunohistochemical study of the β-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. Am. J. Pathol.153, 31–37 (1998). ArticleCASPubMedPubMed Central Google Scholar
Klein, R. S. et al. Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS. J. Immunol.163, 1636–1646 (1999). CASPubMed Google Scholar
Tanabe, S. et al. Murine astrocytes express a functional chemokine receptor. J. Neurosci.17, 6522–6528 (1997). ArticleCASPubMed Google Scholar
Harrison, J. K. et al. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl Acad. Sci. USA95, 10896–10901 (1998). ArticleCASPubMed Google Scholar
Maciejewski-Lenoir, D., Chen, S., Feng, L., Maki, R. & Bacon, K. B. Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. J. Immunol.163, 1628–1635 (1999). CASPubMed Google Scholar
Schwaeble, W. J. et al. Neuronal expression of fractalkine in the presence and absence of inflammation. FEBS Lett.439, 203–207 (1998). ArticleCASPubMed Google Scholar
Meucci, O., Fatatis, A., Simen, A. A. & Miller, R. J. Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc. Natl Acad. Sci. USA97, 8075–8080 (2000). ArticleCASPubMed Google Scholar
Ancuta, P. et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J. Exp. Med.197, 1701–1707 (2003). Highlights the potential role of CX3CL1 in the interaction between different brain cell types and the response to insults in the CNS. ArticleCASPubMedPubMed Central Google Scholar
Zheng, J. et al. Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J. Neuroimmunol.98, 185–200 (1999). ArticleCASPubMed Google Scholar
Schmidtmayerova, H. et al. Human immunodeficiency virus type 1 infection alters chemokine β peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. Proc. Natl Acad. Sci. USA93, 700–704 (1996). ArticleCASPubMed Google Scholar
Sasseville, V. G. et al. Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis. Am. J. Pathol.149, 1459–1467 (1996). CASPubMedPubMed Central Google Scholar
Zink, M. C. et al. Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency virus encephalitis. J. Infect. Dis.184, 1015–1021 (2001). ArticleCASPubMed Google Scholar
Conant, K. et al. Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc. Natl Acad. Sci. USA95, 3117–3121 (1998). ArticleCASPubMed Google Scholar
Kelder, W., McArthur, J. C., Nance-Sproson, T., McClernon, D. & Griffin, D. E. 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 (1998). ArticleCASPubMed Google Scholar
Kaul, M. & Lipton, S. A. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc. Natl Acad. Sci. USA96, 8212–8216 (1999). Indicates a role for the HIV envelope glycoprotein in directly inducing apoptosis of neurons. ArticleCASPubMed Google Scholar
Hesselgesser, J. et al. Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1α is mediated by the chemokine receptor CXCR4. Curr. Biol.8, 595–598 (1998). ArticleCASPubMed Google Scholar
Lazarini, F. et al. Differential signalling of the chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes. Eur. J. Neurosci.12, 117–125 (2000). ArticleCASPubMed Google Scholar
Sanders, V. J., Everall, I. P., Johnson, R. W. & Masliah, E. Fibroblast growth factor modulates HIV coreceptor CXCR4 expression by neural cells. J. Neurosci. Res.59, 671–679 (2000). ArticleCASPubMed Google Scholar
Zheng, J. et al. Lymphotropic virions affect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia. J. Virol.73, 8256–8267 (1999). CASPubMedPubMed Central Google Scholar
Pandey, V. & Bolsover, S. R. Immediate and neurotoxic effects of HIV protein gp120 act through CXCR4 receptor. Biochem. Biophys. Res. Commun.274, 212–215 (2000). ArticleCASPubMed Google Scholar
Ohagen, A. et al. 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 (1999). CASPubMedPubMed Central Google Scholar
Barks, J. D., Liu, X. H., Sun, R. & Silverstein, F. S. gp120, a human immunodeficiency virus-1 coat protein, augments excitotoxic hippocampal injury in perinatal rats. Neuroscience76, 397–409 (1997). ArticleCASPubMed Google Scholar
Xin, K. Q. et al. Evidence of HIV type 1 glycoprotein 120 binding to recombinant _N_-methyl-D-aspartate receptor subunits expressed in a baculovirus system. AIDS Res. Hum. Retroviruses15, 1461–1467 (1999). ArticleCASPubMed Google Scholar
Corasaniti, M. T. et al. Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G. Biochem. Biophys. Res. Commun.274, 664–669 (2000). ArticleCASPubMed Google Scholar
Meucci, O. & Miller, R. J. gp120-induced neurotoxicity in hippocampal pyramidal neuron cultures: protective action of TGF-β1. J. Neurosci.16, 4080–4088 (1996). ArticleCASPubMedPubMed Central Google Scholar
Bezzi, P. et al. CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity. Nature Neurosci.4, 702–710 (2001). ArticleCASPubMed Google Scholar
Garden, G. A. et al. Caspase cascades in human immunodeficiency virus-associated neurodegeneration. J. Neurosci.22, 4015–4024 (2002). ArticleCASPubMed Google Scholar
Klasse, P. J. & Moore, J. P. Is there enough gp120 in the body fluids of HIV-1-infected individuals to have biologically significant effects? Virology323, 1–8 (2004). Recent paper that sheds light and perspective on the conflicting issue of the relevance of manyin vitrostudies to the biological effects of viral proteins. ArticleCASPubMed Google Scholar
Chang, H. C., Samaniego, F., Nair, B. C., Buonaguro, L. & Ensoli, B. HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region. AIDS11, 1421–1431 (1997). ArticleCASPubMed Google Scholar
Andras, I. E. et al. HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. J. Neurosci. Res.74, 255–265 (2003). ArticleCASPubMed Google Scholar
McManus, C. M. et al. Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation. Am. J. Pathol.156, 1441–1453 (2000). ArticleCASPubMedPubMed Central Google Scholar
Park, I. W., Wang, J. F. & Groopman, J. E. HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes. Blood97, 352–358 (2001). ArticleCASPubMed Google Scholar
Song, L., Nath, A., Geiger, J. D., Moore, A. & Hochman, S. Human immunodeficiency virus type 1 Tat protein directly activates neuronal _N_-methyl-D-aspartate receptors at an allosteric zinc-sensitive site. J. Neurovirol.9, 399–403 (2003). ArticleCASPubMed Google Scholar
Sherman, M. P., De Noronha, C. M., Williams, S. A. & Greene, W. C. Insights into the biology of HIV-1 viral protein R. DNA Cell Biol.21, 679–688 (2002). ArticleCASPubMed Google Scholar
Patel, C. A., Mukhtar, M., Harley, S., Kulkosky, J. & Pomerantz, R. J. Lentiviral expression of HIV-1 Vpr induces apoptosis in human neurons. J. Neurovirol.8, 86–99 (2002). ArticleCASPubMed Google Scholar
Patel, C. A., Mukhtar, M. & Pomerantz, R. J. Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells. J. Virol.74, 9717–9726 (2000). ArticleCASPubMedPubMed Central Google Scholar
Levy, D. N., Refaeli, Y. & Weiner, D. B. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J. Virol.69, 1243–1252 (1995). CASPubMedPubMed Central Google Scholar
Marcondes, M. C. et al. 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 (2001). ArticleCASPubMed Google Scholar
Kim, W. K. et al. Identification of T lymphocytes in simian immunodeficiency virus encephalitis: distribution of CD8+ T cells in association with central nervous system vessels and virus. J. Neurovirol.10, 315–325 (2004). ArticleCASPubMed Google Scholar
Glass, J. D., Fedor, H., Wesselingh, S. L. & McArthur, J. C. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann. Neurol.38, 755–762 (1995). ArticleCASPubMed Google Scholar
Achim, C. L., Heyes, M. P. & Wiley, C. A. Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. J. Clin. Invest.91, 2769–2775 (1993). ArticleCASPubMedPubMed Central Google Scholar
Wesselingh, S. L. et al. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann. Neurol.33, 576–582 (1993). ArticleCASPubMed Google Scholar
Adamson, D. C., McArthur, J. C., Dawson, T. M. & Dawson, V. L. Rate and severity of HIV-associated dementia (HAD): correlations with gp41 and iNOS. Mol. Med.5, 98–109 (1999). ArticleCASPubMedPubMed Central Google Scholar
Bukrinsky, M. I. et al. Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. J. Exp. Med.181, 735–745 (1995). ArticleCASPubMed Google Scholar
Blond, D. et al. Nitric oxide synthesis during acute SIVMAC251 infection of macaques. Res. Virol.149, 75–86 (1998). ArticleCASPubMed Google Scholar
Blond, D., Raoul, H., Le Grand, R. & Dormont, D. Nitric oxide synthesis enhances human immunodeficiency virus replication in primary human macrophages. J. Virol.74, 8904–8912 (2000). ArticleCASPubMedPubMed Central Google Scholar
Thompson, K. A., McArthur, J. C. & Wesselingh, S. L. Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Ann. Neurol.49, 745–752 (2001). ArticleCASPubMed Google Scholar
Conant, K. et al. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann. Neurol.46, 391–398 (1999). ArticleCASPubMed Google Scholar
Johnston, J. B. et al. Lentivirus infection in the brain induces matrix metalloproteinase expression: role of envelope diversity. J. Virol.74, 7211–7220 (2000). ArticleCASPubMedPubMed Central Google Scholar
Persidsky, Y. et al. Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFa inhibitor in SCID mice with HIV-1 encephalitis. J. Neuroimmunol.114, 57–68 (2001). ArticleCASPubMed Google Scholar
Stins, M. F. et al. Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors. Lab. Invest.83, 1787–1798 (2003). ArticleCASPubMed Google Scholar
Sasseville, V. G. et al. Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus. Am. J. Pathol.141, 1021–1030 (1992). CASPubMedPubMed Central Google Scholar
Shrikant, P., Benos, D. J., Tang, L. P. & Benveniste, E. N. HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells. Involvement of Janus kinase/signal transducer and activator of transcription and protein kinase C signaling pathways. J. Immunol.156, 1307–1314 (1996). CASPubMed Google Scholar
Grimaldi, L. M. et al. Elevated α-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement. Ann. Neurol.29, 21–25 (1991). ArticleCASPubMed Google Scholar
Wahl, S. M. et al. Macrophage- and astrocyte-derived transforming growth factor-β as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J. Exp. Med.173, 981–991 (1991). ArticleCASPubMed Google Scholar
Tyor, W. R. et al. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann. Neurol.31, 349–360 (1992). ArticleCASPubMed Google Scholar
Nottet, H. S. et al. A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, platelet-activating factor, and tumor necrosis factor-α by activated HIV-1-infected monocytes is attenuated by primary human astrocytes. J. Immunol.154, 3567–3581 (1995). CASPubMed Google Scholar
Wilt, S. G. et al. In vitro evidence for a dual role of tumor necrosis factor-α in human immunodeficiency virus type 1 encephalopathy. Ann. Neurol.37, 381–394 (1995). ArticleCASPubMed Google Scholar
Stoll, G., Jander, S. & Schroeter, M. Cytokines in CNS disorders: neurotoxicity versus neuroprotection. J. Neural Transm. Suppl.59, 81–89 (2000). CASPubMed Google Scholar
Bhat, N. R., Zhang, P., Lee, J. C. & Hogan, E. L. Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-α gene expression in endotoxin-stimulated primary glial cultures. J. Neurosci.18, 1633–1641 (1998). ArticleCASPubMed Google Scholar
Wang, C. X. & Shuaib, A. Involvement of inflammatory cytokines in central nervous system injury. Prog. Neurobiol.67, 161–172 (2002). ArticleCASPubMed Google Scholar
Foos, T. M. & Wu, J. Y. The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis. Neurochem. Res.27, 21–26 (2002). ArticleCASPubMed Google Scholar
Zhang, K. et al. HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nature Neurosci.6, 1064–1071 (2003). ArticleCASPubMed Google Scholar
Cheng, B., Christakos, S. & Mattson, M. P. Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis. Neuron12, 139–153 (1994). ArticleCASPubMed Google Scholar
Barger, S. W. et al. Tumor necrosis factors-α and-β protect neurons against amyloid β-peptide toxicity: evidence for involvement of a κB-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc. Natl Acad. Sci. USA92, 9328–9332 (1995). Describes a neuroprotective role for TNF through activation of anti-oxidant pathways and maintenance of calcium homeostasis. ArticleCASPubMed Google Scholar
Tamatani, M. et al. Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFκB activation in primary hippocampal neurons. J. Biol. Chem.274, 8531–8538 (1999). ArticleCASPubMed Google Scholar
Fontaine, V. et al. Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. J. Neurosci.22, RC216 (2002). ArticlePubMed Google Scholar
Marchetti, L., Klein, M., Schlett, K., Pfizenmaier, K. & Eisel, U. L. Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by _N_-Methyl-D-aspartate receptor activation: essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-κB pathway. J. Biol. Chem.279, 32869–32881 (2004). ArticleCASPubMed Google Scholar
Diem, R., Meyer, R., Weishaupt, J. H. & Bahr, M. Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent AKT phosphorylation by tumor necrosis factor-α rescues axotomized retinal ganglion cells from retrograde cell death in vivo. J. Neurosci.21, 2058–2066 (2001). ArticleCASPubMed Google Scholar
Guo, H. et al. Regulation of β-chemokine mRNA expression in adult rat astrocytes by lipopolysaccharide, proinflammatory and immunoregulatory cytokines. Scand. J. Immunol.48, 502–508 (1998). ArticleCASPubMed Google Scholar
Yoshida, H. et al. Synergistic stimulation, by tumor necrosis factor-α and interferon-γ, of fractalkine expression in human astrocytes. Neurosci. Lett.303, 132–136 (2001). ArticleCASPubMed Google Scholar
Medvedev, A. E., Espevik, T., Ranges, G. & Sundan, A. Distinct roles of the two tumor necrosis factor (TNF) receptors in modulating TNF and lymphotoxin-α effects. J. Biol. Chem.271, 9778–9784 (1996). ArticleCASPubMed Google Scholar
Scorziello, A., Florio, T., Bajetto, A., Thellung, S. & Schettini, G. TGF-β1 prevents gp120-induced impairment of Ca2+ homeostasis and rescues cortical neurons from apoptotic death. J. Neurosci. Res.49, 600–607 (1997). ArticleCASPubMed Google Scholar
da Cunha, A., Jefferson, J. A., Jackson, R. W. & Vitkovic, L. Glial cell-specific mechanisms of TGF-β 1 induction by IL-1 in cerebral cortex. J. Neuroimmunol.42, 71–85 (1993). ArticleCASPubMed Google Scholar
Dragic, T. et al. A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc. Natl Acad. Sci. USA97, 5639–5644 (2000). ArticleCASPubMed Google Scholar
Reeves, J. D. et al. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc. Natl Acad. Sci. USA99, 16249–16254 (2002). ArticleCASPubMed Google Scholar
Hazuda, D. J. et al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science305, 528–532 (2004). ArticleCASPubMed Google Scholar
Toggas, S. M., Masliah, E. & Mucke, L. Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine. Brain Res.706, 303–307 (1996). ArticleCASPubMed Google Scholar
Lipton, S. A. & Chen, H. S. Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine. Cell Death Differ.11, 18–20 (2004). ArticleCASPubMed Google Scholar
Chen, H. S. et al. Neuroprotective concentrations of the _N_-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience86, 1121–1132 (1998). ArticleCASPubMed Google Scholar
Tariot, P. N. et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA291, 317–324 (2004). ArticleCASPubMed Google Scholar
Miguel-Hidalgo, J. J., Alvarez, X. A., Cacabelos, R. & Quack, G. Neuroprotection by memantine against neurodegeneration induced by β-amyloid(1–40). Brain Res.958, 210–221 (2002). ArticleCASPubMed Google Scholar
Ganju, R. K. et al. The α-chemokine, stromal cell-derived factor-1α, binds to the transmembrane G protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways. J. Biol. Chem.273, 23169–23175 (1998). ArticleCASPubMed Google Scholar
Misse, D. et al. HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway. Blood98, 541–547 (2001). ArticleCASPubMed Google Scholar
Martin, D. S. et al. Apoptotic changes in the aged brain are triggered by interleukin-1β-induced activation of p38 and reversed by treatment with eicosapentaenoic acid. J. Biol. Chem.277, 34239–34246 (2002). ArticleCASPubMed Google Scholar
Choi, W. S. et al. Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and -9-mediated apoptotic pathways in dopaminergic neurons. J. Biol. Chem.279, 20451–20460 (2004). ArticleCASPubMed Google Scholar
Song, Y. S. et al. Protective role of Bcl-2 on β-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-κB and p38 MAP kinase activation. Neurosci. Res.49, 69–80 (2004). ArticleCASPubMed Google Scholar
Chen, W. et al. Development of a human neuronal cell model for human immunodeficiency virus (HIV)-infected macrophage-induced neurotoxicity: apoptosis induced by HIV type 1 primary isolates and evidence for involvement of the Bcl-2/Bcl-xL-sensitive intrinsic apoptosis pathway. J. Virol.76, 9407–9419 (2002). ArticleCASPubMedPubMed Central Google Scholar
Brack-Werner, R. Astrocytes: HIV cellular reservoirs and important participants in neuropathogenesis. AIDS13, 1–22 (1999). ArticleCASPubMed Google Scholar
Sabri, F. et al. Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors. Virology264, 370–384 (1999). ArticleCASPubMed Google Scholar
Ranki, A. et al. Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS9, 1001–1008 (1995). ArticleCASPubMed Google Scholar
Codazzi, F. et al. HIV-1 gp120 glycoprotein induces [Ca2+]i responses not only in type-2 but also type-1 astrocytes and oligodendrocytes of the rat cerebellum. Eur. J. Neurosci.7, 1333–1341 (1995). ArticleCASPubMed Google Scholar
Adle-Biassette, H. et al. Neuronal apoptosis in HIV infection in adults. Neuropathol. Appl. Neurobiol.21, 218–227 (1995). ArticleCASPubMed Google Scholar
Gelbard, H. A. et al. Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy. Neuropathol. Appl. Neurobiol.21, 208–217 (1995). ArticleCASPubMed Google Scholar
Petito, C. K. & Roberts, B. Evidence of apoptotic cell death in HIV encephalitis. Am. J. Pathol.146, 1121–1130 (1995). Presents evidence that neuronal apoptosis occurs in the brain in association with HIV infection. CASPubMedPubMed Central Google Scholar