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Feline Immunodeficiency Virus Neuropathogenesis: From Cats to Calcium

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Abstract

Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that have greatly facilitated these efforts. This review summarizes contributions made from in vitro and in vivo studies on the infectious and pathological interactions of feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on FIV have provided insights into the natural progression of CNS disease as well as the contribution of various risk factors. In vitro studies have contributed to our understanding of immune cell trafficking, CNS infection and neuropathogenesis. Together, these studies have made unique contributions to our understanding of (1) lentiviral interactions at the blood–cerebrospinal fluid (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis in the brain, and (3) lentiviral effects on intracellular calcium deregulation and neuronal dysfunction. The ability to combine in vitro and in vivo studies on FIV offers enormous potential to explore neuropathogenic mechanisms and generate information necessary for the development of effective therapeutic interventions.

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References

  • Abramo F, Bo S, Canese MG, Poli A (1995) Regional distribution of lesions in the central nervous system of cats infected with feline immunodeficiency virus. AIDS Res Hum Retrovir 11:1247–1253

    PubMed  CAS  Google Scholar 

  • Ackley CD, Yamamoto JK, Levy N, Pedersen NC, Cooper MD (1990) Immunologic abnormalities in pathogen-free cats experimentally infected with feline immunodeficiency virus. J Virol 64:5652–5655

    PubMed  CAS  Google Scholar 

  • Allison RW, Hoover EA (2003a) Covert vertical transmission of feline immunodeficiency virus. AIDS Res Hum Retrovir 19:421–434

    PubMed  CAS  Google Scholar 

  • Allison RW, Hoover EA (2003b) Feline immunodeficiency virus is concentrated in milk early in lactation. AIDS Res Hum Retrovir 19:245–253

    PubMed  Google Scholar 

  • Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64:529–536

    PubMed  CAS  Google Scholar 

  • Arai M, Earl DD, Yamamoto JK (2002) Is AZT/3TC therapy effective against FIV infection or immunopathogenesis? Vet Immunol Immunopathol 85:189–204

    PubMed  CAS  Google Scholar 

  • Barr MC, Billaud JN, Selway DR, Huitron-Resendiz S, Osborn KG, Henriksen SJ, Phillips TR (2000) Effects of multiple acute morphine exposures on feline immunodeficiency virus disease progression. J Infect Dis 182:725–732

    PubMed  CAS  Google Scholar 

  • Barr MC, Huitron-Resendiz S, Sanchez-Alavez M, Henriksen SJ, Phillips TR (2003) Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers. Drug Alcohol Depend 72:141–149

    PubMed  CAS  Google Scholar 

  • Beebe AM, Dua N, Faith TG, Moore PF, Pedersen NC, Dandekar S (1994) Primary stage of feline immunodeficiency virus infection: viral dissemination and cellular targets. J Virol 68:3080–3091

    PubMed  CAS  Google Scholar 

  • Billaud JN, Selway D, Yu N, Phillips TR (2000) Replication rate of feline immunodeficiency virus in astrocytes is envelope dependent: implications for glutamate uptake. Virology 266:180–188

    PubMed  CAS  Google Scholar 

  • Bisset LR, Lutz H, Boni J, Hofmann-Lehmann R, Luthy R, Schupbach J (2002) Combined effect of zidovudine (ZDV), lamivudine (3TC) and abacavir (ABC) antiretroviral therapy in suppressing in vitro FIV replication. Antiviral Res 53:35–45

    PubMed  CAS  Google Scholar 

  • Boche D, Hurtrel M, Gray F, Claessens-Maire MA, Ganiere JP, Montagnier, Hurtrel B (1996) Virus load and neuropathology in the FIV model. J Neurovirology 2:377–387

    CAS  Google Scholar 

  • Bragg D, Childers T, Tompkins M, Tompkins W, Meeker R (2002a) Infection of the choroid plexus by feline immunodeficiency virus. J Neurovirology 8:211–224

    CAS  Google Scholar 

  • Bragg D, Hudson L, Liang Y, Tompkins M, Fernandes A, Meeker R (2002b) Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus. J Neurovirology 8:225–239

    CAS  Google Scholar 

  • Bragg DC, Boles JC, Meeker RB (2002c) Destabilization of neuronal calcium homeostasis by factors secreted from choroid plexus macrophage cultures in response to feline immunodeficiency virus. Neurobiol Dis 9:173–186

    PubMed  CAS  Google Scholar 

  • Bragg DC, Meeker RB, Duff BA, English RV, Tompkins MB (1999) Neurotoxicity of FIV and FIV envelope protein in feline cortical cultures. Brain Res 816:431–437

    PubMed  CAS  Google Scholar 

  • Brinkmann R, Schwinn A, Muller J, Stahl-Hennig C, Coulibaly C, Hunsmann G, Czub S, Rethwilm A, Dorries R, Ter MV (1993) In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus. Virology 195:561–568

    PubMed  CAS  Google Scholar 

  • Brown WC, Bissey L, Logan KS, Pedersen NC, Elder JH, Collisson EW (1991) Feline immunodeficiency virus infects both CD4+ and CD8+ T lymphocytes. J Virol 65:3359–3364

    PubMed  CAS  Google Scholar 

  • Brunner D, Pedersen NC (1989) Infection of peritoneal macrophages in vitro and in vivo with feline immunodeficiency virus. J Virol 63:5483–5488

    PubMed  CAS  Google Scholar 

  • Bucci JG, English RV, Jordan HL, Childers TA, Tompkins MB, Tompkins WA (1998) Mucosally transmitted feline immunodeficiency virus induces a CD8+ antiviral response that correlates with reduction of cell-associated virus. J Infect Dis 177:18–25

    PubMed  CAS  Google Scholar 

  • Burkhard MJ, Dean GA (2003) Transmission and immunopathogenesis of FIV in cats as a model for HIV. Curr HIV Res 1:15–29

    PubMed  CAS  Google Scholar 

  • Burkhard MJ, Mathiason CK, O’Halloran K, Hoover EA (2002) Kinetics of early FIV infection in cats exposed via the vaginal versus intravenous route. AIDS Res Hum Retrovir 18:217–226

    PubMed  CAS  Google Scholar 

  • Carpenter MA, O’Brien SJ (1995) Coadaptation and immunodeficiency virus: lessons from the Felidae. Curr Opin Genet Dev 5:739–745

    PubMed  CAS  Google Scholar 

  • Chen H, Wood C, Petito CK (2000) Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis. J Neurovirology 6:498–506

    CAS  Google Scholar 

  • Cloak CC, Chang L, Ernst T, Barr MC, Huitron-Resendiz S, Sanchez-Alavez M, Phillips TR, Henriksen S (2004) Methamphetamine and AIDS: 1HMRS studies in a feline model of human disease. J Neuroimmunol 147:16–20

    PubMed  CAS  Google Scholar 

  • Cysique LA, Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, Brown S, Atkinson JH, Clifford DB, Simpson D, Torres G, Hall C, Power C, Marder K, McArthur JC, Symonds W, Romero C (2005) Undetectable cerebrospinal fluid HIV RNA and beta-2 microglobulin do not indicate inactive AIDS dementia complex in highly active antiretroviral therapy-treated patients. J Acquir Immune Defic Syndr 39:426–429

    PubMed  CAS  Google Scholar 

  • D’Cruz OJ, Waurzyniak B, Uckun FM (2004) Antiretroviral spermicide WHI-07 prevents vaginal and rectal transmission of feline immunodeficiency virus in domestic cats. Antimicrob Agents Chemother 48:1082–1088

    PubMed  CAS  Google Scholar 

  • Danave IR, Tiffany Castiglioni E, Zenger E, Barhoumi R, Burghardt RC, Collisson EW (1994) Feline immunodeficiency virus decreases cell–cell communication and mitochondrial membrane potential. J Virol 68:6745–6750

    PubMed  CAS  Google Scholar 

  • de Parseval A, Chatterji U, Sun P, Elder JH (2004) Feline immunodeficiency virus targets activated CD4+ T cells by using CD134 as a binding receptor. Proc Natl Acad Sci USA 101:13044–13049

    PubMed  Google Scholar 

  • de Ronde A, Stam JG, Boers P, Langedijk H, Meloen R, Hesselink W, Keldermans LC, van Vliet A, Verschoor EJ, Horzinek MC (1994) Antibody response in cats to the envelope proteins of feline immunodeficiency virus: identification of an immunodominant neutralization domain. Virology 198:257–264

    PubMed  Google Scholar 

  • de Rozieres S, Swan CH, Sheeter DA, Clingerman KJ, Lin YC, Huitron-Resendiz S, Henriksen S, Torbett BE, Elder JH (2004) Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3. Retrovirology 1:38

    PubMed  Google Scholar 

  • Del Mauro D, Matteucci D, Giannecchini S, Maggi F, Pistello M, Bendinelli M (1998) Autologous and heterologous neutralization analyses of primary feline immunodeficiency virus isolates. J Virol 72:2199–2207

    PubMed  Google Scholar 

  • Dou H, Birusingh K, Faraci J, Gorantla S, Poluektova LY, Maggirwar SB, Dewhurst S, Gelbard HA, Gendelman HE (2003) Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci 23:9162–9170

    PubMed  CAS  Google Scholar 

  • Dow S, Poss M, Hoover E (1990) Feline immunodeficiency virus: a neurotropic lentivirus. J AIDS 3:658–668

    CAS  Google Scholar 

  • Dow SW, Dreitz MJ, Hoover EA (1992) Feline immunodeficiency virus neurotropism: evidence that astrocytes and microglia are the primary target cells. Vet Immunol Immunopathol 35:23–35

    PubMed  CAS  Google Scholar 

  • Dow SW, Mathiason CK, Hoover EA (1999) In vivo monocyte tropism of pathogenic feline immunodeficiency viruses. J Virol 73:6852–6861

    PubMed  CAS  Google Scholar 

  • Egberink H, Borst M, Niphuis H, Balzarini J, Neu H, Schellekens H, De Clercq E, Horzinek M, Koolen M (1990) Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine. Proc Natl Acad Sci USA 87:3087–3091

    PubMed  CAS  Google Scholar 

  • Egberink HF, De Clercq E, van Vliet AL, Balzarini J, Bridger GJ, Henson G, Horzinek MC, Schols D (1999) Bicyclams, selective antagonists of the human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication. J Virol 73:6346–6352

    PubMed  CAS  Google Scholar 

  • Elder JH, Phillips TR (1993) Molecular properties of feline immunodeficiency virus (FIV). Infect Agents Dis 2:361–374

    PubMed  CAS  Google Scholar 

  • Ellis RJ, Gamst AC, Capparelli E, Spector SA, Hsia K, Wolfson T, Abramson I, Grant I, McCutchan JA (2000) Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54:927–936

    PubMed  CAS  Google Scholar 

  • English R, Johnson C, Gebhard DH, Tompkins MB (1993) In vivo lymphocyte tropism of feline immunodeficiency virus. J Virol 67:5175–5186

    PubMed  CAS  Google Scholar 

  • English RV, Nelson P, Johnson CM, Nasisse M, Tompkins WA, Tompkins MB (1994) Development of clinical disease in cats experimentally infected with feline immunodeficiency virus. J Infect Dis 170:543–552

    PubMed  CAS  Google Scholar 

  • Epstein LG, Gelbard HA (1999) HIV-1-induced neuronal injury in the developing brain. J Leukoc Biol 65:453–457

    PubMed  CAS  Google Scholar 

  • Falangola MF, Hanly A, Galvao-Castro B, Petito CK (1995) HIV infection of human choroid plexus: a possible mechanism of viral entry into the CNS. J Neuropathol Exp Sci 54:497–503

    CAS  Google Scholar 

  • Fine SM, Angel RA, Perry SW, Epstein LG, Rothstein JD, Dewhurst S, Gelbard HA (1996) Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. J Biol Chem 271:15303–15306

    PubMed  CAS  Google Scholar 

  • Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L’Heureux D, Regulier EG, Richardson MW, Amini S, Morgello S, Khalili K, Rappaport J (2001) CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirology 7:528–541

    CAS  Google Scholar 

  • Garg H, Fuller FJ, Tompkins WA (2004) Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion. Virology 321:274–286

    PubMed  CAS  Google Scholar 

  • Gavrilin MA, Mathes LE, Podell M (2002) Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes. J Neurovirology 8:240–249

    CAS  Google Scholar 

  • Gebhard DH, Dow JL, Childers TA, Alvelo JI, Tompkins MB, Tompkins WA (1999) Progressive expansion of an l-selectin-negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats. J Infect Dis 180:1503–1513

    PubMed  CAS  Google Scholar 

  • Gemignani A, Paudice P, Pittaluga A, Raiteri M (2000) The HIV-1 coat protein gp120 and some of its fragments potently activate native cerebral NMDA receptors mediating neuropeptide release. Eur J Neurosci 12:2839–2846

    PubMed  CAS  Google Scholar 

  • Gendelman HE, Lipton SA, Epstein LG, Swindells S (2005) The Neurology of AIDS, 2nd edn.: Oxford University Press

    Google Scholar 

  • Giulian D, Vaca K, Noonan CA (1990) Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science 250:1593–1596

    PubMed  CAS  Google Scholar 

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

    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

    PubMed  CAS  Google Scholar 

  • Gruol DL, Yu N, Parsons KL, Billaud JN, Elder JH, Phillips TR (1998) Neurotoxic effects of feline immunodeficiency virus, FIV-PPR. J Neurovirology 4:415–425

    CAS  Google Scholar 

  • Hartmann K, Donath A, Beer B, Egberink HF, Horzinek MC, Lutz H, Hoffmann-Fezer G, Thum I, Thefeld S (1992) Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms. Vet Immunol Immunopathol 35:167–175

    PubMed  CAS  Google Scholar 

  • Haughey NJ, Holden CP, Nath A, Geiger JD (1999) Involvement of inositol 1,4,5-trisphosphate-regulated stores of intracellular calcium in calcium dysregulation and neuron cell death caused by HIV-1 protein tat. J Neurochem 73:1363–1374

    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

    PubMed  CAS  Google Scholar 

  • Hayes KA, Wilkinson JG, Frick R, Francke S, Mathes LE (1995) Early suppression of viremia by ZDV does not alter the spread of feline immunodeficiency virus infection in cats. J Acquir Immune Defic Syndr Hum Retrovirol 9:114–122

    PubMed  CAS  Google Scholar 

  • Hegg CC, Thayer SA (1999) Monocytic cells secrete factors that evoke excitatory synaptic activity in rat hippocampal cultures. Eur J Pharmacol 385:231–237

    PubMed  CAS  Google Scholar 

  • Hein A, Martin JP, Dorries R (2001) In vitro activation of feline immunodeficiency virus in ramified microglial cells from asymptomatically infected cats. J Virol 75:8090–8095

    PubMed  CAS  Google Scholar 

  • Hein A, Martin JP, Koehren F, Bingen A, Dorries R (2000) In vivo infection of ramified microglia from adult cat central nervous system by feline immunodeficiency virus. Virology 268:420–429

    PubMed  CAS  Google Scholar 

  • Hoffmann-Fezer G, Thum J, Ackley C, Herbold M, Mysliwietz J, Thefeld S, Hartmann K, Kraft W (1992) Decline in CD4+ cell numbers in cats with naturally acquired feline immunodeficiency virus infection. J Virol 66:1484–1488

    PubMed  CAS  Google Scholar 

  • Hohdatsu T, Fujimori S, Maeki M, Suma N, Motokawa K, Okada S, Koyama H (1997) Virus neutralizing antibody titer to feline immunodeficiency virus isolates of subtypes A, B and D in experimentally or naturally infected cats. J Vet Med Sci 59:377–381

    PubMed  CAS  Google Scholar 

  • Hohdatsu T, Miyagawa N, Ohkubo M, Kida K, Koyama H (2000) Studies on feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus (FIV) activity. Arch Virol 145:2525–2538

    PubMed  CAS  Google Scholar 

  • Hohdatsu T, Sasagawa T, Yamazaki A, Motokawa K, Kusuhara H, Kaneshima T, Koyama H (2002) CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro. Arch Virol 147:1517–1529

    PubMed  CAS  Google Scholar 

  • Holden CP, Haughey NJ, Nath A, Geiger JD (1999) Role of Na+/H+ exchangers, excitatory amino acid receptors and voltage-operated Ca2+ channels in human immunodeficiency virus type 1 gp120-mediated increases in intracellular Ca2+ in human neurons and astrocytes. Neuroscience 91:1369–1378

    PubMed  CAS  Google Scholar 

  • Hosie MJ, Broere N, Hesselgesser J, Turner JD, Hoxie JA, Neil JC, Willett BJ (1998) Modulation of feline immunodeficiency virus infection by stromal cell-derived factor. J Virol 72:2097–2104

    PubMed  CAS  Google Scholar 

  • Huang C, Conlee D, Loop J, Champ D, Gill M, Chu HJ (2004) Efficacy and safety of a feline immunodeficiency virus vaccine. Anim Health Res Rev 5:295–300

    PubMed  Google Scholar 

  • Hudson LC, Bragg DC, Tompkins MB, Meeker RB (2005) Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells. Brain Res 1058:148–160

    PubMed  CAS  Google Scholar 

  • Hurtrel M, Ganiere J, Guelifi J, Chakrabarti L, Maire M, Gray F, Montagnier L, Hurtrel B (1992) Comparison of early and late feline immunodeficiency virus encephalopathies. AIDS 6:399–406

    PubMed  CAS  Google Scholar 

  • Jacobson S, Henricksen SJ, Prospero-Garcia O, Phillips TR, Elder JH, Young WG, Bloom FE, Fox HS (1997) Cortical neuronal cytoskeletal changes associated with FIV infection. Journal Neurovirology 3:283–289

    CAS  Google Scholar 

  • Johnston JB, Power C (2002) Feline immunodeficiency virus xenoinfection: the role of chemokine receptors and envelope diversity. J Virol 76:3626–3636

    PubMed  CAS  Google Scholar 

  • Jones G, Power C (2006) Regulation of neural cell survival by HIV-1 infection. Neurobiol Dis 21:1–17

    PubMed  CAS  Google Scholar 

  • Jordan HL, Howard JG, Bucci JG, Butterworth JL, English R, Kennedy-Stoskopf S, Tompkins MB, Tompkins WA (1998) Horizontal transmission of feline immunodeficiency virus with semen from seropositive cats. J Reprod Immunol 41:341–357

    PubMed  CAS  Google Scholar 

  • Kanki PJ, McLane MF, King NW Jr, Letvin NL, Hunt RD, Sehgal P, Daniel MD, Desrosiers RC, Essex M (1985) Serologic identification and characterization of a macaque T-lymphotropic retrovirus closely related to HTLV-III. Science 228:1199–1201

    PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Maeda K, Tohya Y, Furuya T, Miyazawa T, Horimoto T, Norimine J, Kai C, Mikami T (1992) Replicative difference in early-passage feline brain cells among feline immunodeficiency virus isolates. Arch Virol 125:347–354

    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

    PubMed  CAS  Google Scholar 

  • Koirala TR, Nakagaki K, Ishida T, Nonaka S, Morikawa S, Tabira T (2001) Decreased expression of MAP-2 and GAD in the brain of cats infected with feline immunodeficiency virus. Tohoku J Exp Med 195:141–151

    PubMed  CAS  Google Scholar 

  • Kolson DL (2002) Neuropathogenesis of central nervous system HIV-1 infection. Clin Lab Med 22:703–717

    PubMed  Google Scholar 

  • Kovacs EM, Baxter GD, Robinson WF (1999) Feline peripheral blood mononuclear cells express message for both CXC and CC type chemokine receptors. Arch Virol 144:273–285

    PubMed  CAS  Google Scholar 

  • Lane JH, Sasseville VG, Smith MO, Vogel P, Pauley DR, Heyes MP, Lackner AA (1996) Neuroinvasion by simian immunodeficiency virus coincides with increased numbers of perivascular macrophages/microglia and intrathecal immune activation. J Neurovirology 2:423–432

    CAS  Google Scholar 

  • Lerner DL, Elder JH (2000) Expanded host cell tropism and cytopathic properties of feline immunodeficiency virus strain PPR subsequent to passage through interleukin-2-independent T cells. J Virol 74:1854–1863

    PubMed  CAS  Google Scholar 

  • Levy JA (1993) Pathogenesis of human immunodeficiency virus infection. Microbiol Rev 57:183–289

    PubMed  CAS  Google Scholar 

  • Lipton S (1992) Models of neuronal injury in AIDS: another role for the NMDA receptor? TINS 15:75–80

    PubMed  CAS  Google Scholar 

  • Lipton S, Sucher N, Kaiser P, Dreyer E (1991) Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity. Neuron 7:111–118

    PubMed  CAS  Google Scholar 

  • Liu P, Hudson LC, Tompkins MB, Vahlenkamp TW, Colby B, Rundle C, Meeker RB (2006a) Cerebrospinal fluid is an efficient route for establishing brain infection with feline immunodeficiency virus and transferring infectious virus to the periphery. J Neurovirology 12:294–306

    Google Scholar 

  • Liu P, Hudson LC, Tompkins MB, Vahlenkamp TW, Meeker RB (2006b) Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation. J Neurovirology 12:307–321

    CAS  Google Scholar 

  • Livingstone WJ, Moore M, Innes D, Bell JE, Simmonds P (1996) Frequent infection of peripheral blood CD8-positive T-lymphocytes with HIV-1. Edinburgh Heterosexual Transmission Study Group. Lancet 348:649–654

    PubMed  CAS  Google Scholar 

  • Lo TK, Fallert CJ, Piser TM, Thayer SA (1992) HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons. Brain Res 594:189–196

    PubMed  CAS  Google Scholar 

  • Lombardi S, Massi C, Tozzini F, Zaccaro L, Bazzichi A, Bandecchi P, La Rosa C, Bendinelli M, Garzelli C (1995) Epitope mapping of the V3 domain of feline immunodeficiency virus envelope glycoprotein by monoclonal antibodies. J Gen Virol 76 (Pt 8):1893–1899

    PubMed  CAS  Google Scholar 

  • Macchi S, Maggi F, Di Iorio C, Poli A, Bendinelli M, Pistello M (1998) Detection of feline immunodeficiency proviral sequences in lymphoid tissues and the central nervous system by in situ gene amplification. J Virol Methods 73:109–119

    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

    PubMed  CAS  Google Scholar 

  • McArthur JC, Brew BJ, Nath A (2005) Neurological complications of HIV infection. Lancet Neurol 4:543–555

    PubMed  Google Scholar 

  • Meeker R, English R, Tompkins M (1996) Enhanced excitotoxicity in primary feline neural cultures exposed to feline immunodeficiency virus (FIV). J Neuro-AIDS 1:1–27

    Google Scholar 

  • Meeker RB, Azuma Y, Bragg DC, English RV, Tompkins M (1999a) Microglial proliferation in cortical neural cultures exposed to feline immunodeficiency virus. J Neuroimmunol 101:15–26

    PubMed  CAS  Google Scholar 

  • Meeker RB, Boles JC, Robertson KR, Hall CD (2005) Cerebrospinal fluid from human immunodeficiency virus-infected individuals facilitates neurotoxicity by suppressing intracellular calcium recovery. J Neurovirology 11:144–156

    CAS  Google Scholar 

  • Meeker RB, Robertson K, Barry T, Hall C (1999b) Neurotoxicity of CSF from HIV-infected humans. J Neurovirology 5:507–518

    CAS  Google Scholar 

  • Meeker RB, Thiede BA, Hall C, English R, Tompkins M (1997) Cortical cell loss in asymptomatic cats experimentally infected with feline immunodeficiency virus. AIDS Res Hum Retrovir 13:1131–1140

    Article  PubMed  CAS  Google Scholar 

  • Mitchell TW, Buckmaster PS, Hoover EA, Whalen LR, Dudek FE (1999) Neuron loss and axon reorganization in the dentate gyrus of cats infected with the feline immunodeficiency virus. J Comp Neurol 411:563–577

    PubMed  CAS  Google Scholar 

  • Nagra RM, Masliah E, Wiley CA (1993) Synaptic and dendritic pathology in murine retroviral encephalitis. Exp Neurol 124:283–288

    PubMed  CAS  Google Scholar 

  • Nakagaki K, Nakagaki K, Takahashi K, Schols D, De Clercq E, Tabira T (2001) CXCR4 is the primary receptor for feline immunodeficiency virus in astrocytes. J Neurovirology 7:487–492

    CAS  Google Scholar 

  • Neuenburg JK, Brodt HR, Herndier BG, Bickel M, Bacchetti P, Price RW, Grant RM, Schlote W (2002) 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

    PubMed  Google Scholar 

  • Novotney C, English R, Housman J, Davidson M, Nasisse M, Jeng CR, Davis W, Tompkins M (1990) Lymphocyte population changes in cats naturally infected with feline immunodeficiency virus. AIDS 4:1213–1218

    PubMed  CAS  Google Scholar 

  • O’Neil LL, Burkhard MJ, Hoover EA (1996) Frequent perinatal transmission of feline immunodeficiency virus by chronically infected cats. J Virol 70:2894–2901

    PubMed  CAS  Google Scholar 

  • Obert LA, Hoover EA (2002) Early pathogenesis of transmucosal feline immunodeficiency virus infection. J Virol 76:6311–6322

    PubMed  CAS  Google Scholar 

  • Olmsted R, Hirsch V, Purcell R, Johnson P (1989) Nucleotide sequence analysis of feline immunodeficiency virus:genome organization and relationship to other lentiviruses. Proc Natl Acad Sci 86:8088–8092

    PubMed  CAS  Google Scholar 

  • Osborne R, Rigby M, Siebelink K, Neil JC, Jarrett O (1994) Virus neutralization reveals antigenic variation among feline immunodeficiency virus isolates. J Gen Virol 75 (Pt 12):3641–3645

    PubMed  CAS  Google Scholar 

  • Pedersen NC, Ho EW, Brown ML, Yamamoto JK (1987) Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 235:790–793

    PubMed  CAS  Google Scholar 

  • Perry SW, Norman JP, Gelbard HA (2005) Adjunctive therapies for HIV-1 associated neurologic disease. Neurotox Res 8:161–166

    PubMed  CAS  Google Scholar 

  • Persidsky Y, Stins M, Way D, Witte MH, Weinand M, Kim KS, Bock P, Gendelman HE, Fiala M (1997) A model for monocyte migration through the blood–brain barrier during HIV-1 encephalitis. J Immunol 158:3499–3510

    PubMed  CAS  Google Scholar 

  • Petito CK (2004) Human immunodeficiency virus type 1 compartmentalization in the central nervous system. J Neurovirology 10 Suppl 1:21–24

    CAS  Google Scholar 

  • Petito CK, Chen H, Mastri AR, Torres-Munoz J, Roberts B, Wood C (1999) HIV infection of choroid plexus in AIDS and asymptomatic HIV-infected patients suggests that the choroid plexus may be a reservoir of productive infection. J Neurovirology 5:670–677

    CAS  Google Scholar 

  • Phillips T, Prospero-Garcia O, Puaoi D, Lerner D, Fox H, Olmsted R, Bloom F, Heriksen S, Elder J (1994) Neurological abnormalities associated with feline immunodeficiency virus infection. J Gen Virol 75:979–987

    PubMed  CAS  Google Scholar 

  • Phillips TR, Prospero-Garcia O, Wheeler DW, Wagaman P, Lerner DL, Fox HS, Whalen LR, Bloom FE, Elder JH, Henricksen SJ (1996) Neurologic dysfunctions caused by a molecular clone of feline immunodeficiency virus, FIV-PPR. J Neurovirology 2:388–396

    CAS  Google Scholar 

  • Phipps AJ, Hayes KA, Buck WR, Podell M, Mathes LE (2000) Neurophysiologic and immunologic abnormalities associated with feline immunodeficiency virus molecular clone FIV-PPR DNA inoculation. J Acquir Immune Defic Syndr 23:8–16

    PubMed  CAS  Google Scholar 

  • Pistello M, Menzo S, Giorgi M, Da Prato L, Cammarota G, Clementi M, Bendinelli M (1994) Competitive polymerase chain reaction for quantitating feline immunodeficiency virus load in infected cat tissues. Mol Cell Probes 8:229–234

    PubMed  CAS  Google Scholar 

  • Podell M, Hayes K, Oglesbee M, Mathes L (1997) Progressive encephalopathy associated with CD4/CD8 inversion in adult FIV-infected cats. J Acquir Immune Defic Syndr Hum Retrovirol 15:332–340

    PubMed  CAS  Google Scholar 

  • Podell M, Maruyama K, Smith M, Hayes KA, Buck WR, Ruehlmann DS, Mathes LE (1999) Frontal lobe neuronal injury correlates to altered function in FIV-infected cats. J Acquir Immune Defic Syndr 22:10–18

    PubMed  CAS  Google Scholar 

  • Podell M, Oglesbee M, Mathes L, Krakowka S, Olmstead R, Lafrado L (1993) AIDS-associated encephalopathy with experimental feline immunodeficiency virus Infection. J AIDS 6:758–771

    CAS  Google Scholar 

  • Poli A, Abramo F, Di Iorio C, Cantile C, Carli MA, Pollera C, Vago L, Tosoni A, Costanzi G (1997) Neuropathology in cats experimentally infected with feline immunodeficiency virus: a morphological, immunocytochemical and morphometric study. J Neurovirology 3:361–368

    Article  CAS  Google Scholar 

  • Poli A, Pistello M, Carli MA, Abramo F, Mancuso G, Nicoletti E, Bendinelli M (1999) Tumor necrosis factor-alpha and virus expression in the central nervous system of cats infected with feline immunodeficiency virus. J Neurovirology 5:465–473

    CAS  Google Scholar 

  • Potter SJ, Dwyer DE, Saksena NK (2003) Differential cellular distribution of HIV-1 drug resistance in vivo: evidence for infection of CD8+ T cells during HAART. Virology 305:339–352

    PubMed  CAS  Google Scholar 

  • Power C, Buist R, Johnston JB, Del Bigio MR, Ni W, Dawood MR, Peeling J (1998) Neurovirulence in feline immunodeficiency virus-infected neonatal cats is viral strain specific and dependent on systemic immune suppression. J Virol 72:9109–9115

    PubMed  CAS  Google Scholar 

  • Power C, Moench T, Peeling J, Kong PA, Langelier T (1997) Feline immunodeficiency virus causes increased glutamate levels and neuronal loss in brain. Neuroscience 77:1175–1185

    PubMed  CAS  Google Scholar 

  • Prospero-Garcia O, Herold N, Phillips T, Elder J, Bloom F, Henriksen S (1994) Sleep patterns are disturbed in cats infected with feline immunodeficiency virus. Proc Natl Acad Sci 91:12947–12951

    PubMed  CAS  Google Scholar 

  • Pu R, Coleman J, Omori M, Arai M, Hohdatsu T, Huang C, Tanabe T, Yamamoto JK (2001) Dual-subtype FIV vaccine protects cats against in vivo swarms of both homologous and heterologous subtype FIV isolates. AIDS 15:1225–1237

    PubMed  CAS  Google Scholar 

  • Pulliam L, Herndier BG, Tang NM, McGrath MS (1991) Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. J Clin Invest 87:503–512

    PubMed  CAS  Google Scholar 

  • Richardson J, Fossati I, Moraillon A, Castelot S, Sonigo P, Pancino G (1996) Neutralization sensitivity and accessibility of continuous B cell epitopes of the feline immunodeficiency virus envelope. J Gen Virol 77 (Pt 4):759–771

    PubMed  CAS  Google Scholar 

  • Richardson J, Pancino G, Merat R, Leste-Lasserre T, Moraillon A, Schneider-Mergener J, Alizon M, Sonigo P, Heveker N (1999) Shared usage of the chemokine receptor CXCR4 by primary and laboratory-adapted strains of feline immunodeficiency virus. J Virol 73:3661–3671

    PubMed  CAS  Google Scholar 

  • Ryan G, Grimes T, Brankin B, Mabruk MJ, Hosie MJ, Jarrett O, Callanan JJ (2005) Neuropathology associated with feline immunodeficiency virus infection highlights prominent lymphocyte trafficking through both the blood–brain and blood–choroid plexus barriers. J Neurovirology 11:337–345

    CAS  Google Scholar 

  • Ryan G, Klein D, Knapp E, Hosie MJ, Grimes T, Mabruk MJ, Jarrett O, Callanan JJ (2003) Dynamics of viral and proviral loads of feline immunodeficiency virus within the feline central nervous system during the acute phase following intravenous infection. J Virol 77:7477–7485

    PubMed  CAS  Google Scholar 

  • Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirology 8:136–142

    Google Scholar 

  • Self RL, Mulholland PJ, Nath A, Harris BR, Prendergast MA (2004) The human immunodeficiency virus type-1 transcription factor Tat produces elevations in intracellular Ca2+ that require function of an N-methyl-d-aspartate receptor polyamine-sensitive site. Brain Res 995:39–45

    PubMed  CAS  Google Scholar 

  • Shimojima M, Miyazawa T, Ikeda Y, McMonagle EL, Haining H, Akashi H, Takeuchi Y, Hosie MJ, Willett BJ (2004) Use of CD134 as a primary receptor by the feline immunodeficiency virus. Science 303:1192–1195

    PubMed  CAS  Google Scholar 

  • Siebelink KH, Bosch ML, Rimmelzwaan GF, Meloen RH, Osterhaus AD (1995) Two different mutations in the envelope protein of feline immunodeficiency virus allow the virus to escape from neutralization by feline serum antibodies. Vet Immunol Immunopathol 46:51–59

    PubMed  CAS  Google Scholar 

  • Silvotti L, Corradi A, Brandi G, Cabassi A, Bendinelli M, Magnan M, Piedimonte G (1997) FIV induced encephalopathy: early brain lesions in the absence of viral replication in monocyte/macrophages. A pathogenetic model. Vet Immunol Immunopathol 55:263–271

    PubMed  CAS  Google Scholar 

  • Steffan AM, Lafon ME, Gendrault JL, Koehren F, De Monte M, Royer C, Kirn A, Gut JP (1994) Feline immunodeficiency virus can productively infect cultured endothelial cells from cat brain microvessels. J Gen Virol 75:3647–3653

    Article  PubMed  CAS  Google Scholar 

  • Steffen BJ, Breier G, Butcher EC, Schulz M, Engelhardt B (1996) ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. Am J Pathol 148:1819–1838

    PubMed  CAS  Google Scholar 

  • Steigerwald ES, Sarter M, March P, Podell M (1999) Effects of feline immunodeficiency virus on cognition and behavioral function in cats. J Acquir Immune Defic Syndr Hum Retrovirol 20:411–419

    PubMed  CAS  Google Scholar 

  • Strain MC, Letendre S, Pillai SK, Russell T, Ignacio CC, Gunthard HF, Good B, Smith DM, Wolinksy SM, Furtado M, Marquie-Beck J, Durelle J, Grant I, Richman DD, Marcotte T, McCutchan JA, Ellis RJ, Wong JK (2005) Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy. J Virol 79:1772–1788

    PubMed  CAS  Google Scholar 

  • Talbott RL, Sparger EE, Lovelace KM, Fitch WM, Pedersen NC, Luciw PA, Elder JH (1989) Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci USA 86:5743–5747

    PubMed  CAS  Google Scholar 

  • Toggas SM, Masliah E, Mucke L (1996) 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

    PubMed  CAS  Google Scholar 

  • Tompkins MB, Nelson PD, English RV, Novotney C (1991) Early events in the immunopathogenesis of feline retrovirus infections. JAVMA 199:1311–1315

    PubMed  CAS  Google Scholar 

  • Torten M, Franchini M, Barlough JE, George JW, Mozes E, Lutz H, Pedersen NC (1991) Progressive immune dysfunction in cats experimentally infected with feline immunodeficiency virus. J Virol 65:2225–2230

    PubMed  CAS  Google Scholar 

  • Turchan J, Sacktor N, Wojna V, Conant K, Nath A (2003) Neuroprotective therapy for HIV dementia. Curr HIV Res 1:373–383

    PubMed  CAS  Google Scholar 

  • Tymianski M (1996) Cytosolic calcium concentrations and cell death in vitro. Adv Neurol 71:85–105

    PubMed  CAS  Google Scholar 

  • Tymianski M, Charlton MP, Carlen PL, Tator CH (1993) Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons. J Neurosci 13:2085–2104

    PubMed  CAS  Google Scholar 

  • Uhl EW, Heaton-Jones TG, Pu R, Yamamoto JK (2002) FIV vaccine development and its importance to veterinary and human medicine: a review FIV vaccine 2002 update and review. Vet Immunol Immunopathol 90:113–132

    PubMed  CAS  Google Scholar 

  • Vahlenkamp TW, Tompkins MB, Tompkins WA (2005) The role of CD4+CD25+ regulatory T cells in viral infections. Vet Immunol Immunopathol 108:219–225

    PubMed  CAS  Google Scholar 

  • Wasmoen T, Armiger-Luhman S, Egan C, Hall V, Chu HJ, Chavez L, Acree W (1992) Transmission of feline immunodeficiency virus from infected queens to kittens. Vet Immunol Immunopathol 35:83–93

    PubMed  CAS  Google Scholar 

  • Wiley C, 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

    PubMed  CAS  Google Scholar 

  • Willett BJ, Cannon CA, Hosie MJ (2002) Upregulation of surface feline CXCR4 expression following ectopic expression of CCR5: implications for studies of the cell tropism of feline immunodeficiency virus. J Virol 76:9242–9252

    PubMed  CAS  Google Scholar 

  • Willett BJ, Hosie MJ, Callanan JJ, Neil JC, Jarrett O (1993) Infection with feline immunodeficiency virus is followed by the rapid expansion of a CD8+ lymphocyte subset. Immunology 78:1–6

    PubMed  CAS  Google Scholar 

  • Willett BJ, Picard L, Hosie MJ, Turner JD, Adema K, Clapham PR (1997) Shared usage of the chemokine receptor CXCR4 by the feline and human immunodeficiency viruses. J Virol 71:6407–6415

    PubMed  CAS  Google Scholar 

  • Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, Alvarez X, Lackner AA (2001) 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

    PubMed  CAS  Google Scholar 

  • Xiong H, Zheng J, Thylin M, Gendelman HE (1999) Unraveling the mechanisms of neurotoxicity in HIV type 1-associated dementia: inhibition of neuronal synaptic transmission by macrophage secretory products. AIDS Res Hum Retrovir 15:57–63

    PubMed  CAS  Google Scholar 

  • Yeh MW, Kaul M, Zheng J, Nottet HS, Thylin M, Gendelman HE, Lipton SA (2000) Cytokine-stimulated, but not HIV-infected, human monocyte-derived macrophages produce neurotoxic levels of l-cysteine. J Immunol 164:4265–4270

    PubMed  CAS  Google Scholar 

  • Yu N, Billaud JN, Phillips TR (1998) Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases. Proc Natl Acad Sci USA 95:2624–2629

    PubMed  CAS  Google Scholar 

  • Zenger E, Collisson EW, Barhoumi R, Burghardt RC, Danave IR, Tiffany-Castiglioni E (1995) Laser cytometric analysis of FIV-induced injury in astroglia. Glia 13:92–100

    PubMed  CAS  Google Scholar 

  • Zenger E, Tiffany-Castiglioni E, Collisson EW (1997) Cellular mechanisms of feline immunodeficiency virus (FIV)-induced neuropathogenesis. Front Biosci 2:d527–d537

    PubMed  CAS  Google Scholar 

  • Zheng J, Ghorpade A, Niemann D, Cotter RL, Thylin MR, Epstein L, Swartz JM, Shepard RB, Liu X, Nukuna A, Gendelman HE (1999a) Lymphotropic virions affect chemokine receptor-mediated neural signaling and apoptosis: implications for human immunodeficiency virus type 1-associated dementia. J Virol 73:8256–8267

    PubMed  CAS  Google Scholar 

  • Zheng J, Thylin MR, Cotter RL, Lopez AL, Ghorpade A, Persidsky Y, Xiong H, Leisman GB, Che MH, Gendelman HE (2001) HIV-1 infected and immune competent mononuclear phagocytes induce quantitative alterations in neuronal dendritic arbor: relevance for HIV-1-associated dementia. Neurotox Res 3:443–459

    Article  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 (1999b) Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol 98:185–200

    PubMed  CAS  Google Scholar 

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Acknowledgment

This study was supported by NIMH Grant R01 MH063646.

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Meeker, R.B. Feline Immunodeficiency Virus Neuropathogenesis: From Cats to Calcium. Jrnl Neuroimmune Pharm 2, 154–170 (2007). https://doi.org/10.1007/s11481-006-9045-z

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