Skip to main content

Advertisement

SpringerLink
Log in

When Human Immunodeficiency Virus Meets Chemokines and Microglia: Neuroprotection or Neurodegeneration?

  • INVITED REVIEW
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

Chemokines are chemotactic cytokines that were originally discovered as promoters of leukocyte proliferation and mobility. In recent years, however, evidence has demonstrated constitutive expression of chemokines and chemokine receptors in a variety of cells in the central and peripheral nervous system and has proposed a role for chemokines in neurodegenerative diseases characterized by inflammation and microglia proliferation. In addition, chemokine receptors, and in particular CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV) infection of immunocompetent cells as well as microglia. Subsequently, HIV, through a variety of mechanisms, promotes synapto-dendritic alterations and neuronal loss that ultimately lead to motor and cognitive impairments. These events are accompanied by microglia activation. Nevertheless, a microglia-mediated mechanism of neuronal degeneration alone cannot fully explain some of the pathological features of HIV infected brain such as synaptic simplification. In this article, we present evidence that some of the microglia responses to HIV are beneficial and neuroprotective. These include the ability of microglia to release anti-inflammatory cytokines, to remove dying cells and to promote axonal sprouting.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adler MW, Rogers TJ (2005) Are chemokines the third major system in the brain? J Leukoc Biol 78:1204–1209

    Article  PubMed  CAS  Google Scholar 

  • Ahmed F, MacArthur L, De Bernardi MA, Mocchetti I (2009) Retrograde and anterograde transport of HIV protein gp120 in the nervous system. Brain Behav Immun 23:355–364

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Albright AV, Soldan SS, Gonzalez-Scarano F (2003) Pathogenesis of human immunodeficiency virus-induced neurological disease. J Neurovirol 9:222–227

    PubMed  CAS  Google Scholar 

  • Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA (1996) CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272:1955–1958

    Article  PubMed  CAS  Google Scholar 

  • Anderson E, Zink W, Xiong H, Gendelman HE (2002) HIV-1-associated dementia: a metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes. J Acquir Immune Defic Syndr 31(Suppl 2):S43–S54

    Article  PubMed  CAS  Google Scholar 

  • Aramori I, Zhang J, Ferguson SSG, Bieniasz PD, Cullen BR, Caron MG (1997) Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor. EMBO J 16:4606–4616

    Article  PubMed  CAS  Google Scholar 

  • Argyris EG, Acheampong E, Nunnari G, Mukhtar M, Williams KJ, Pomerantz RJ (2003) 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

    Article  PubMed  CAS  Google Scholar 

  • Avdoshina V, Biggio F, Palchik G, Campbell LA, Mocchetti I (2010) Morphine induces the release of CCL5 from astrocytes: potential neuroprotective mechanism against the HIV protein gp120. Glia 58:1630–1639

    PubMed  Google Scholar 

  • Avdoshina V, Becker J, Campbell L, Parsadanian M, Mhyre T, Tessarollo L, Mocchetti I (2011) Neurotrophins modulate the expression of chemokine receptors in the brain. J Neurovirol 17:58–62

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Major EO, Mocchetti I (2003) Brain-derived neurotrophic factor inhibits human immunodeficiency virus-1/gp120-mediated cerebellar granule cell death by preventing gp120 internalization. J Neurosci 23:5715–5722

    PubMed  CAS  Google Scholar 

  • Bachis A, Aden SA, Nosheny RL, Andrews PM, Mocchetti I (2006) Axonal transport of Human Immunodeficiency Virus Type 1 envelope glycoprotein 120 is found in association with neuronal apoptosis. J Neurosci 26:6771–6780

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Biggio F, Major EO, Mocchetti I (2009) M- and T-tropic HIVs promote apoptosis in rat neurons. J Neuroimmune Pharmacol 4:150–160

    Article  PubMed  Google Scholar 

  • Bachis A, Cruz MI, Mocchetti I (2010) M-tropic HIV envelope protein gp120 exhibits a different neuropathological profile than T-tropic gp120 in rat striatum. Eur J Neurosci 32:570–578

    Article  PubMed  Google Scholar 

  • Bagetta G, Corasaniti MT, Berliocchi L, Navarra M, Finazzi-Agro A, Nistico G (1995) HIV-1 gp120 produces DNA fragmentation in the cerebral cortex of rat. Biochem Biophys Res Commun 211:130–136

    Article  PubMed  CAS  Google Scholar 

  • Banisadr G, Fontanges P, Haour F, Kitabgi P, Rostene W, Parsadaniantz SM (2002) Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Eur J Neurosci 16:1661–1671

    Article  PubMed  Google Scholar 

  • Banisadr G, Skrzydelski D, Kitabgi P, Rostene W, Parsadaniantz SM (2003) Highly regionalized distribution of stromal cell-derived factor-1/CXCL12 in adult rat brain: constitutive expression in cholinergic, dopaminergic and vasopressinergic neurons. Eur J Neurosci 18:1593–1606

    Article  PubMed  Google Scholar 

  • Bansal AK, Mactutus CF, Nath A, Maragos W, Hauser KF, Booze RM (2000) Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum. Brain Res 879:42–49

    Article  PubMed  CAS  Google Scholar 

  • Batchelor PE, Porritt MJ, Martinello P, Parish CL, Liberatore GT, Donnan GA, Howells DW (2002) Macrophages and microglia produce local trophic gradients that stimulate axonal sprouting toward but not beyond the wound edge. Mol Cell Neurosci 21:436–453

    Article  PubMed  CAS  Google Scholar 

  • Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385:640–644

    Article  PubMed  CAS  Google Scholar 

  • Berger JR, Arendt G (2000) HIV dementia: The role of the basal ganglia and dopaminergic systems. J Psychopharmacol 14:214–221

    Article  PubMed  CAS  Google Scholar 

  • Berger JR, Kumar M, Kumar A, Fernandez JB, Levin B (1994) Cerebrospinal fluid dopamine in HIV-1 infection. AIDS 8:67–71

    Article  PubMed  CAS  Google Scholar 

  • Berson JF, Long D, Doranz BJ, Rucker J, Jirik FR, Doms RW (1996) A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol 70:6288–6295

    PubMed  CAS  Google Scholar 

  • Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J, Volterra A (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710

    Article  PubMed  CAS  Google Scholar 

  • Bobardt MD, Salmon P, Wang L, Esko JD, Gabuzda D, Fiala M, Trono D, Van der Schueren B, David G, Gallay PA (2004) Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J Virol 78:6567–6584

    Article  PubMed  CAS  Google Scholar 

  • Bomsel M (1997) Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nat Med 3:42–47

    Article  PubMed  CAS  Google Scholar 

  • Brandoli C, Sanna A, De Bernardi MA, Follesa P, Brooker G, Mocchetti I (1998) Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. J Neurosci 18:7953–7961

    PubMed  CAS  Google Scholar 

  • Bruce-Keller AJ, Chauhan A, Dimayuga FO, Gee J, Keller JN, Nath A (2003) Synaptic transport of human immunodeficiency virus-Tat protein causes neurotoxicity and gliosis in rat brain. J Neurosci 23:8417–8422

    PubMed  CAS  Google Scholar 

  • Bruno V, Copani A, Besong G, Scoto G, Nicoletti F (2000) Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta-amyloid-induced toxicity in culture. Eur J Pharmacol 399:117–121

    Article  PubMed  CAS  Google Scholar 

  • Buckner CM, Calderon TM, Willams DW, Belbin TJ, Berman JW (2011) Characterization of monocyte maturation/differentiation that facilitates their transmigration across the blood brain barrier and infection by HIV: Implications for NeuroAIDS. Cell Immunol 267:109–123

    Article  PubMed  CAS  Google Scholar 

  • Budka H (1986) Multinucleated giant cells in brain: a hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol 69:253–258

    Article  PubMed  CAS  Google Scholar 

  • Budka H (1991) Neuropathology of human immunodeficiency virus infection. Brain Pathol 1:163–175

    Article  PubMed  CAS  Google Scholar 

  • Callewaere C, Fernette B, Raison D, Mechighel P, Burlet A, Calas A, Kitabgi P, Parsadaniantz SM, Rostene W (2008) Cellular and subcellular evidence for neuronal interaction between the chemokine stromal cell-derived factor-1/CXCL 12 and vasopressin: regulation in the hypothalamo-neurohypophysial system of the Brattleboro rats. Endocrinology 149:310–319

    Article  PubMed  CAS  Google Scholar 

  • Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee J-C, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924

    Article  PubMed  CAS  Google Scholar 

  • Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48:16–42

    Article  PubMed  CAS  Google Scholar 

  • Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B, Wes P, Ransohoff RM, Gan L (2011) CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. J Biol Chem 286:32713–32722

    Article  PubMed  CAS  Google Scholar 

  • Colton CA, Wilcock DM (2010) Assessing activation states in microglia. CNS Neurol Disord Drug Targets 9:174–191

    Article  PubMed  CAS  Google Scholar 

  • Conant K, Tornatore C, Atwood W, Meyers K, Traub R, Major EO (1994) In vivo and in vitro infection of the astrocyte by HIV-1. Adv Neuroimmunol 4:287–289

    Article  PubMed  CAS  Google Scholar 

  • 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 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci U S A 95:3117–3121

    Article  PubMed  CAS  Google Scholar 

  • Cosenza-Nashat MA, Bauman A, Zhao ML, Morgello S, Suh HS, Lee SC (2011) Cannabinoid receptor expression in HIV encephalitis and HIV-associated neuropathologic comorbidities. Neuropath Appl Neurobiol 37:464–483

    Article  CAS  Google Scholar 

  • Cristiani SA, Pukay-Martin ND, Bornstein RA (2004) Marijuana use and cognitive function in HIV-infected people. J Neuropsychiatry Clin Neurosci 16:330–335

    Article  PubMed  Google Scholar 

  • Dash PK, Gorantla S, Gendelman HE, Knibbe J, Casale GP, Makarov E, Epstein AA, Gelbard HA, Boska MD, Poluektova LY (2011) Loss of neuronal integrity during progressive HIV-1 infection of humanized mice. J Neurosci 31:3148–3157

    Article  PubMed  CAS  Google Scholar 

  • Davies J, Everall IP, Weich S, McLaughlin J, Scaravilli F, Lantos PL (1997) HIV-associated brain pathology in the United Kingdom: an epidemiological study. AIDS 11:1145–1150

    Article  PubMed  CAS  Google Scholar 

  • Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O’Brien SJ (1996) Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 273:1856–1862

    Article  PubMed  CAS  Google Scholar 

  • De Clercq E (2003) The bicyclam AMD3100 story. Nat Rev Drug Discov 2:581–587

    Article  PubMed  CAS  Google Scholar 

  • de Jong EK, Vinet J, Stanulovic VS, Meijer M, Wesseling E, Sjollema K, Boddeke HW, Biber K (2008) Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles. FASEB J 22:4136–4145

    Article  PubMed  CAS  Google Scholar 

  • Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666

    Article  PubMed  CAS  Google Scholar 

  • di Rocco A, Bottiglieri T, Dorfman D, Werner P, Morrison C, Simpson DA (2000) Decreased homovanilic acid in cerebrospinal fluid correlates with impaired neuropsychologic function in HIV-1-infected patients. Clin Neuropharmacol 23:190–194

    Article  PubMed  Google Scholar 

  • Dittmar MT, McKnight A, Simmons G, Clapham PR, Weiss RA, Simmonds P (1997) HIV-1 tropism and co-receptor use. Nature 385:495–496

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW (1996) A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85:1149–1158

    Article  PubMed  CAS  Google Scholar 

  • 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 chemokine receptor CC-CKR-5. Nature 381:667–673

    Article  PubMed  CAS  Google Scholar 

  • Dunfee R, Thomas ER, Gorry PR, Wang J, Ancuta P, Gabuzda D (2006a) Mechanisms of HIV-1 neurotropism. Curr HIV Res 4:267–278

    Article  PubMed  CAS  Google Scholar 

  • Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, Wolinsky SM, Gabuzda D (2006b) The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci USA 103:15160–15165

    Article  PubMed  CAS  Google Scholar 

  • Edelstein H, Knight RT (1987) Severe parkinsonism in two AIDS patients taking prochlorperazine. Lancet 2:341–342

    Article  PubMed  CAS  Google Scholar 

  • Edo-Matas D, van Dort KA, Setiawan LC, Schuitemaker H, Kootstra NA (2011) Comparison of in vivo and in vitro evolution of CCR5 to CXCR4 coreceptor use of primary human immunodeficiency virus type 1 variants. Virology 412:269–277

    Article  PubMed  CAS  Google Scholar 

  • Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44

    Article  PubMed  CAS  Google Scholar 

  • Escola JM, Kuenzi G, Gaertner H, Foti M, Hartley O (2010) CC chemokine receptor 5 (CCR5) desensitization: cycling receptors accumulate in the trans-Golgi network. J Biol Chem 285:41772–41780

    Article  PubMed  CAS  Google Scholar 

  • Eugenin EA, King JE, Nath A, Calderon TM, Zukin RS, Bennett MVL, Berman JW (2007) HIV-tat induces formation of an LRP-PSD-95-NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci USA 104:3438–3443

    Article  PubMed  CAS  Google Scholar 

  • Eugenin EA, Clements JE, Zink MC, Berman JW (2011) Human immunodeficiency virus infection of human astrocytes disrupts blood-brain barrier integrity by a gap junction-dependent mechanism. J Neurosci 31:9456–9465

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, Hudson L, Al-Sarraj S, Honavar M, Lantos P, Kerwin R (1995) Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity. Nat Med 1:1174–1178

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, Hansen LA, Masliah E (2005) The shifting patterns of HIV encephalitis neuropathology. Neurotox Res 8:51–61

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 10:872–877

    Article  Google Scholar 

  • Fiedorowicz A, Figiel I, Zaremba M, Dzwonek K, Oderfeld-Nowak B (2008) The ameboid phenotype of NG2 (+) cells in the region of apoptotic dentate granule neurons in trimethyltin intoxicated mice shares antigen properties with microglia/macrophages. Glia 56:209–222

    Article  PubMed  Google Scholar 

  • Fischer-Smith T, Croul S, Adeniyi A, Rybicka K, Morgello S, Khalili K, Rappaport J (2004) 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

    Article  PubMed  CAS  Google Scholar 

  • Fox L, Alford M, Achim C, Mallory M, Masliah E (1997) Neurodegeneration of somatostatin-immunoreactive neurons in HIV encephalitis. J Neuropathol Exp Neurol 56:360–368

    Article  PubMed  CAS  Google Scholar 

  • Gabuzda D, He J, Ohagen A, Vallat AV (1998) Chemokine receptors in HIV-1 infection of the central nervous system. Semin Immunol 10:203–213

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Gendelman HE, Baca LM, Husayni H, Turpin JA, Skillman D, Kalter DC, Orenstein JM, Hoover DL, Meltzer MS (1990) Macrophage-HIV interaction: viral isolation and target cell tropism. AIDS 4:221–228

    Article  PubMed  CAS  Google Scholar 

  • Goldman JP, Blundell MP, Lopes L, Kinnon C, Di Santo JP, Thrasher AJ (1998) Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor γ chain. Br J Haematol 103:335–342

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gorry PR, Bristol G, Zack JA, Ritola K, Swanstrom R, Birch CJ, Bell JE, Bannert N, Crawford K, Wang H, Schols D, De Clercq E, Kunstman K, Wolinsky SM, Gabuzda D (2001) Macrophage tropism of human immunodeficiency virus Type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity. J Virol 75:10073–10089

    Article  PubMed  CAS  Google Scholar 

  • Gorry PR, Taylor J, Holm GH, Mehle A, Morgan T, Cayabyab M, Farzan M, Wang H, Bell JE, Kunstman K, Moore JP, Wolinsky SM, Gabuzda D (2002) Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate. J Virol 76:6277–6292

    Article  PubMed  CAS  Google Scholar 

  • Gouwy M, Struyf S, Berghmans N, Vanormelingen C, Schols D, Van Damme J (2011) CXCR4 and CCR5 ligands cooperate in monocyte and lymphocyte migration and in inhibition of dual-tropic (R5/X4) HIV-1 infection. Eur J Immunol 41:963–973

    Article  PubMed  CAS  Google Scholar 

  • Graeber MB (2010) Changing face of microglia. Science 330:783–788

    Article  PubMed  CAS  Google Scholar 

  • Guyon A, Banisadr G, Rovere C, Cervantes A, Kitabgi P, Melik-Parsadaniantz S, Nahon JL (2005) Complex effects of stromal cell-derived factor-1 alpha on melanin-concentrating hormone neuron excitability. Eur J Neurosci 21:701–710

    Article  PubMed  CAS  Google Scholar 

  • Hatori K, Nagai A, Heisel R, Ryu JK, Kim SU (2002) Fractalkine and fractalkine receptors in human neurons and glial cells. J Neurosci Res 69:418–426

    Article  PubMed  CAS  Google Scholar 

  • Haughey NJ, Nath A, Mattson MP, Slevin JT, Geiger JD (2001) HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. J Neurochem 78:457–467

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Horch HW (2004) Local effects of BDNF on dendritic growth. Rev Neurosci 15:117–129

    PubMed  CAS  Google Scholar 

  • Hriso E, Kuhn T, Masdeu JC, Grundman M (1991) Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy. Am J Psychiatry 148:1558–1561

    PubMed  CAS  Google Scholar 

  • Hu QX, Barry AP, Wang ZX, Connolly SM, Peiper SC, Greenberg ML (2000) Evolution of the human immunodeficiency virus type 1 envelope during infection reveals molecular corollaries of specificity for coreceptor utilization and AIDS pathogenesis. J Virol 74:11858–11872

    Article  PubMed  CAS  Google Scholar 

  • Ioannidis JP, Reichlin S, Skolnik PR (1995) Long-term productive human immunodeficiency virus-1 infection in human infant microglia. Am J Pathol 147:1200–1206

    PubMed  CAS  Google Scholar 

  • Itoh K, Mehraein P, Weis S (2000) Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathol (Berl) 99:376–384

    Article  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kaul M, Ma Q, Medders KE, Desai MK, Lipton SA (2007) HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ 14:296–305

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kondru R, Zhang J, Ji C, Mirzadegan T, Rotstein D, Sankuratri S, Dioszegi M (2008) Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists. Mol Pharmacol 73:789–800

    Article  PubMed  CAS  Google Scholar 

  • Koning FA, Schols D, Schuitemaker H (2001) No selection for CCR5 coreceptor usage during parenteral transmission of macrophagetropic syncytium-inducing human immunodeficiency virus type 1. J Virol 75:8848–8853

    Article  PubMed  CAS  Google Scholar 

  • Koutsilieri E, Sopper S, Scheller C, ter Meulen V, Riederer P (2002) Parkinsonism in HIV dementia. J Neural Transm 109:767–775

    Article  PubMed  CAS  Google Scholar 

  • Kramer-Hammerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R (2005) Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res 111:194–213

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Li W, Galey D, Mattson MP, Nath A (2005) Molecular and cellular mechanisms of neuronal cell death in HIV dementia. Neurotox Res 8:119–134

    Article  PubMed  CAS  Google Scholar 

  • Liu NQ, Lossinsky AS, Popik W, Li X, Gujuluva C, Kriederman B, Roberts J, Pushkarsky T, Bukrinsky M, Witte M, Weinand M, Fiala M (2002) 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

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Liu H, Kim BO, Gattone VH, Li J, Nath A, Blum J, He JJ (2004) CD4-independent infection of astrocytes by human immunodeficiency virus Type 1: requirement for the human mannose receptor. J Virol 78:4120–4133

    Article  PubMed  CAS  Google Scholar 

  • Lucas M, Stuart LM, Zhang A, Hodivala-Dilke K, Febbraio M, Silverstein R, Savill J, Lacy-Hulbert A (2006) Requirements for apoptotic cell contact in regulation of macrophage responses. J Immunol 177:4047–4054

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Mandrekar S, Jiang Q, Lee CY, Koenigsknecht-Talboo J, Holtzman DM, Landreth GE (2009) Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis. J Neurosci 29:4252–4262

    Article  PubMed  CAS  Google Scholar 

  • Marini AM, Rabin SJ, Lipsky RH, Mocchetti I (1998) Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate. J Biol Chem 273:29394–29399

    Article  PubMed  CAS  Google Scholar 

  • Marini AM, Jiang X, Wu X, Pan H, Guo Z, Mattson MP, Blondeau N, Novelli A, Lipsky RH (2007) Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli. Amino Acids 32:299–304

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Ge N, Mucke L (1996) Pathogenesis of HIV-1 associated neurodegeneration. Crit Rev Neurobiol 10:57–67

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Heaton RK, Marcotte TD, Ellis RJ, Wiley CA, Mallory M, Achim CL, McCutchan JA, Nelson JA, Atkinson JH, Grant I (1997) Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center. Ann Neurol 42:963–972

    Article  PubMed  CAS  Google Scholar 

  • Mazurier F, Fontanellas A, Salesse S, Taine L, Landriau S, Moreau-Gaudry F, Reiffers J, Peault B, Santo JPD, Verneuil HD (1999) A novel immunodeficient mouse model-RAG2 gamma cytokine receptor chain double mutants-requiring exogenous cytokine administration for human hematopoietic stem cell engraftment common. J Interferon Cytokine Res 19:533–541

    Article  PubMed  CAS  Google Scholar 

  • McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157:3–10

    Article  PubMed  CAS  Google Scholar 

  • McCarthy M, He J, Auger D, Geffin R, Woodson C, Hutto C, Wood C, Scott G (2002) Cellular tropisms and co-receptor usage of HIV-1 isolates from vertically infected children with neurological abnormalities and rapid disease progression. J Med Virol 67:1–8

    Article  PubMed  Google Scholar 

  • Medders KE, Sejbuk NE, Maung R, Desai MK, Kaul M (2010) Activation of p38 MAPK is required in monocytic and neuronal cells for HIV glycoprotein 120-induced neurotoxicity. J Immunol 185:4883–4895

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Musante V, Longordo F, Neri E, Pedrazzi M, Kalfas F, Severi P, Raiteri M, Pittaluga A (2008) RANTES modulates the release of glutamate in human neocortex. J Neurosci 28:12231–12240

    Article  PubMed  CAS  Google Scholar 

  • Naif HM, Cunningham AL, Alali M, Li S, Nasr N, Buhler MM, Schols D, de Clercq E, Stewart G (2002) A human immunodeficiency virus type 1 isolate from an infected person homozygous for CCR5Delta32 exhibits dual tropism by infecting macrophages and MT2 cells via CXCR4. J Virol 76:3114–3124

    Article  PubMed  CAS  Google Scholar 

  • Nath A, Berger J (2004) HIV dementia. Curr Treat Options Neurol 6:139–151

    Article  PubMed  Google Scholar 

  • Nath A, Conant K, Chen P, Scott C, Major EO (1999) Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon. J Biol Chem 274:17098–17102

    Article  PubMed  CAS  Google Scholar 

  • Nath A, Maragos WF, Avison MJ, Schmitt FA, Berger JR (2001) Acceleration of HIV dementia with methamphetamine and cocaine. J Neurovirol 7:66–71

    Article  PubMed  CAS  Google Scholar 

  • Nicolai J, Burbassi S, Rubin J, Meucci O (2010) CXCL12 inhibits expression of the NMDA receptor’s NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival. Cell Death Dis 1:e33

    Article  PubMed  CAS  Google Scholar 

  • Nikolaev A, McLaughlin T, O’Leary DDM, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981–989

    Article  PubMed  CAS  Google Scholar 

  • Nosheny RL, Bachis A, Acquas E, Mocchetti I (2004) Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain-derived neurotrophic factor in vivo: potential implication for neuronal cell death. Eur J Neurosci 20:2857–2864

    Article  PubMed  Google Scholar 

  • Pantaleo G, Fauci AS (1995) Apoptosis in HIV infection. Nat Med 1:118–120

    Article  PubMed  CAS  Google Scholar 

  • Patel CA, Mukhtar M, Pomerantz RJ (2000) Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells. J Virol 74:9717–9726

    Article  PubMed  CAS  Google Scholar 

  • Paxton WA, Martin SR, Tse D, O’Brien TR, Skurnick J, VanDevanter NL, Padian N, Braun JF, Kotler DP, Wolinsky SM, Koup RA (1996) Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med 2:412–417

    Article  PubMed  CAS  Google Scholar 

  • Persidsky Y, Gendelman HE (2003) Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J Leukoc Biol 74:691–701

    Article  PubMed  CAS  Google Scholar 

  • Peter C, Wesselborg S, Herrmann M, Lauber K (2010) Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells. Apoptosis 15:1007–1028

    Article  PubMed  Google Scholar 

  • Petito CK, Roberts B, Cantando JD, Rabinstein A, Duncan R (2001) Hippocampal injury and alterations in neuronal chemokine co-receptor expression in patients with AIDS. J Neuropathol Exp Neurol 60:377–385

    PubMed  CAS  Google Scholar 

  • Piller SC, Ewart GD, Premkumar A, Cox GB, Gage PW (1996) Vpr protein of human immunodeficiency virus type 1 forms cation-selective channels in planar lipid bilayers. Proc Natl Acad Sci U S A 93:111–115

    Article  PubMed  CAS  Google Scholar 

  • Power C, McArthur JC, Johnson RT, Griffin DE, Glass JD, Perryman S, Chesebro B (1994) Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol 68:4643–4649

    PubMed  CAS  Google Scholar 

  • Radja F, Kay DG, Albrecht S, Jolicoeur P (2003) Oligodendrocyte-specific expression of human immunodeficiency virus type 1 Nef in transgenic mice leads to vacuolar myelopathy and alters oligodendrocyte phenotype in vitro. J Virol 77:11745–11753

    Article  PubMed  CAS  Google Scholar 

  • Rao JS, Kim HW, Kellom M, Greenstein D, Chen M, Kraft AD, Harry GJ, Rapoport SI, Basselin M (2011) Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. J Neuroinflammation 8:101

    Article  PubMed  CAS  Google Scholar 

  • Raymond S, Delobel P, Mavigner M, Cazabat M, Encinas S, Souyris C, Bruel P, Sandres-Saune K, Marchou B, Massip P, Izopet J (2010) CXCR4-using viruses in plasma and peripheral blood mononuclear cells during primary HIV-1 infection and impact on disease progression. AIDS 24:2305–2312

    PubMed  CAS  Google Scholar 

  • Reid W et al (2001) An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci U S A 98:9271–9276

    Article  PubMed  CAS  Google Scholar 

  • Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991) Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathol (Berl) 82:39–44

    Article  CAS  Google Scholar 

  • Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc 10:1–14

    Article  PubMed  CAS  Google Scholar 

  • Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242

    Article  PubMed  CAS  Google Scholar 

  • Rostene W, Kitabgi P, Parsadaniantz SM (2007) Chemokines: a new class of neuromodulator? Nat Rev Neurosci 8:895–903

    Article  PubMed  CAS  Google Scholar 

  • Saini V, Marchese A, Tang W-J, Majetschak M (2011) Structural determinants of the ubiquitin-CXC chemokine receptor 4 interaction. J Biol Chem

  • Sardar AM, Czudek C, Reynolds GP (1996) Dopamine deficits in the brain: the neurochemical basis of parkinsonian symptoms in AIDS. Neuroreport 7:910–912

    Article  PubMed  CAS  Google Scholar 

  • Scarlatti G, Tresoldi E, Bjorndal A, Fredriksson R, Colognesi C, Deng HK, Malnati MS, Plebani A, Siccardi AG, Littman DR, Fenyo EM, Lusso P (1997) In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med 3:1259–1265

    Article  PubMed  CAS  Google Scholar 

  • Sharer LR, Cho ES, Epstein LG (1985) Multinucleated giant cells and HTLV-III in AIDS encephalopathy. Hum Pathol 16:760

    Article  PubMed  CAS  Google Scholar 

  • Shimoji M, Pagan F, Healton EB, Mocchetti I (2009) CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson’s disease. Neurotox Res 16:318–328

    Article  PubMed  CAS  Google Scholar 

  • Simmons G, Reeves JD, McKnight A, Dejucq N, Hibbitts S, Power CA, Aarons E, Schols D, De Clercq E, Proudfoot AE, Clapham PR (1998) CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages. J Virol 72:8453–8457

    PubMed  CAS  Google Scholar 

  • Singh A, Yi Y, Isaacs SN, Kolson DL, Collman RG (2001) Concordant utilization of macrophage entry coreceptors by related variants within an HIV type 1 primary isolate viral swarm. AIDS Res Hum Retroviruses 17:957–963

    Article  PubMed  CAS  Google Scholar 

  • Singh IN, Goody RJ, Dean C, Ahmad NM, Lutz SE, Knapp PE, Nath A, Hauser KF (2004) Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G. J Neurovirol 10:141–151

    Article  PubMed  CAS  Google Scholar 

  • Skrzydelski D, Guyon A, Daugé V, Rovère C, Apartis E, Kitabgi P, Nahon JL, Rostène W, Parsadaniantz SM (2007) The chemokine stromal cell-derived factor-1/CXCL12 activates the nigrostriatal dopamine system. J Neurochem 102:1175–1183

    Article  PubMed  CAS  Google Scholar 

  • Sozzani S, Introna M, Bernasconi S, Polentarutti N, Cinque P, Poli G, Sica A, Mantovani A (1997) MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression. J Leukoc Biol 62:30–33

    PubMed  CAS  Google Scholar 

  • Stefanova N, Fellner L, Reindl M, Masliah E, Poewe W, Wenning G (2011) Toll-Like receptor 4 promotes synuclein clearance and survival of nigral dopaminergic neurons. Am J Pathol 179:954–963

    Article  PubMed  CAS  Google Scholar 

  • Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Hollt V, Schulz S (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: Isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865–5878

    PubMed  CAS  Google Scholar 

  • Sui Y, Stehno-Bittel L, Li S, Loganathan R, Dhillon NK, Pinson D, Nath A, Kolson D, Narayan O, Buch S (2006) CXCL10-induced cell death in neurons: role of calcium dysregulation. Eur J Neurosci 23:957–964

    Article  PubMed  Google Scholar 

  • Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GC, Kasai H (2008) Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319:1683–1687

    Article  PubMed  CAS  Google Scholar 

  • Tarasova NI, Stauber RH, Michejda CJ (1998) Spontaneous and ligand-induced trafficking of CXC-chemokine receptor 4. J Biol Chem 273:15883–15886

    Article  PubMed  CAS  Google Scholar 

  • Thomas ER, Dunfee RL, Stanton J, Bogdan D, Taylor J, Kunstman K, Bell JE, Wolinsky SM, Gabuzda D (2007) Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion. Virology 360:105–119

    Article  PubMed  CAS  Google Scholar 

  • Thompson KA, Cherry CL, Bell JE, McLean CA (2011) Brain cell reservoirs of latent virus in presymptomatic HIV-Infected individuals. Am J Pathol 179:1623–1629

    Article  PubMed  CAS  Google Scholar 

  • Toggas SM, Masliah E, Rockenstein EM, Rall GF, Abraham CR, Mucke L (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 367:188–193

    Article  PubMed  CAS  Google Scholar 

  • Tornatore C, Chandra R, Berger JR, Major EO (1994a) HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44:481–487

    Article  PubMed  CAS  Google Scholar 

  • Tornatore C, Meyers K, Atwood W, Conant K, Major E (1994b) Temporal patterns of human immunodeficiency virus type 1 transcripts in human fetal astrocytes. J Virol 68:93–102

    PubMed  CAS  Google Scholar 

  • Trecki J, Brailoiu GC, Unterwald EM (2010) Localization of CXCR4 in the forebrain of the adult rat. Brain Res 1315:53–62

    Article  PubMed  CAS  Google Scholar 

  • Trillo-Pazos G, McFarlane-Abdulla E, Campbell IC, Pilkington GJ, Everall IP (2000) Recombinant nef HIV-IIIB protein is toxic to human neurons in culture. Brain Res 864:315–326

    Article  PubMed  CAS  Google Scholar 

  • Tuttle DL, Anders CB, Aquino-De Jesus MJ, Poole PP, Lamers SL, Briggs DR, Pomeroy SM, Alexander L, Peden KW, Andiman WA, Sleasman JW, Goodenow MM (2002) Increased replication of non-syncytium-inducing HIV type 1 isolates in monocyte-derived macrophages is linked to advanced disease in infected children. AIDS Res Hum Retroviruses 18:353–362

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Wang G-J, Chang L, Volkow ND, Telang F, Logan J, Ernst T, Fowler JS (2004) Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain 127:2452–2458

    Article  PubMed  Google Scholar 

  • Watkins BA, Dorn HH, Kelly WB, Armstrong RC, Potts BJ, Michaels F, Kufta CV, Dubois-Dalcq M (1990) Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science 249:549–553

    Article  PubMed  CAS  Google Scholar 

  • Weissman D, Rabin RL, Arthos J, Rubbert A, Dybul M, Swofford R, Venkatesan S, Farber JM, Fauci AS (1997) Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor. Nature 389:981–985

    Article  PubMed  CAS  Google Scholar 

  • Westmoreland SV, Alvarez X, deBakker C, Aye P, Wilson ML, Williams KC, Lackner AA (2002) Developmental expression patterns of CCR5 and CXCR4 in the rhesus macaque brain. J Neuroimmunol 122:146–158

    Article  PubMed  CAS  Google Scholar 

  • Wiley CA, Achim C (1994) Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome. Ann Neurol 36:673–676

    Article  PubMed  CAS  Google Scholar 

  • Yong VW (2005) Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 6:931–944

    Article  PubMed  CAS  Google Scholar 

  • Yong VW, Rivest S (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron 64:55–60

    Article  PubMed  CAS  Google Scholar 

  • Zegarra-Moran O, Rasola A, Rugolo M, Porcelli AM, Rossi B, Galietta LJ (1999) HIV-1 nef expression inhibits the activity of a Ca2+ -dependent K+ channel involved in the control of the resting potential in CEM lymphocytes. J Immunol 162:5359–5366

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD (1993) Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179–1181

    Article  PubMed  CAS  Google Scholar 

  • Zlotnik A, Yoshie O, Nomiyama H (2006) The chemokine and chemokine receptor superfamilies and their molecular evolution. Genome Biol 7:243

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Institute of Drug Abuse 1R01DA026174 and 1F31DA032282, and National Institute of Neurological Disorders and Stroke 1R21NS074916 and the Intramural Research Program of the National Institute of Environmental Health Sciences. The authors have no conflict of interest to declare. The views expressed in this article are those of the authors and they do not represent the views or policies of the National Toxicology Program or National Institute of Environmental Health Sciences.

Author information

Authors and Affiliations

  1. Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC, 20057, USA

    Italo Mocchetti, Lee A. Campbell & Valeriya Avdoshina

  2. National Toxicology Program Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC, 27709, USA

    G. Jean Harry

Authors
  1. Italo Mocchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lee A. Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Jean Harry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valeriya Avdoshina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Italo Mocchetti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mocchetti, I., Campbell, L.A., Harry, G.J. et al. When Human Immunodeficiency Virus Meets Chemokines and Microglia: Neuroprotection or Neurodegeneration?. J Neuroimmune Pharmacol 8, 118–131 (2013). https://doi.org/10.1007/s11481-012-9353-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-012-9353-4

Keywords

Search

Navigation