Top

Published in:

01-12-2013 | Immunology & Microbiology in Miami

Innate immune responses to HIV infection in the central nervous system

Authors: Rebeca Geffin, Micheline McCarthy

Published in: Immunologic Research | Issue 1-3/2013

Abstract

Human immunodeficiency virus (HIV) invades the brain early during infection and generates a chronic inflammatory microenvironment that can eventually result in neurological disease, even in the absence of significant viral replication. Thus, HIV-1 infection of the brain has been characterized both as a neuroimmunological and neurodegenerative disorder. While the brain and central nervous system (CNS) have historically been regarded as immune privileged or immunologically quiescent, newer concepts of CNS immunity suggest an important if not defining role for innate immune responses generated by glial cells. Innate immunity may be the first line of defense against HIV infection of the brain and CNS, with multiple cellular elements providing responses that can be anti-viral and neuroprotective, but also potentially neurotoxic, impairing neurogenesis and promoting neuronal apoptosis. To investigate the effects of HIV exposure on neurogenesis and neuronal survival, we have studied the responses of human neuroepithelial progenitor (NEP) cells, which undergo directed differentiation into astrocytes and neurons in vitro. We identified a group of genes that were differentially expressed in NEP-derived cells during virus exposure. This included genes that are strongly related to interferon-induced responses and antigen presentation. Moreover, we observed that the host factor apolipoprotein E influences the innate immune response expressed by these cells, with a more robust response in the apolipoprotein E3/E3 genotype cultures compared to the apolipoprotein E3/E4 counterparts. Thus, neuroepithelial progenitors and their differentiated progeny recognize HIV and respond to it by mounting an innate immune response with a vigor that is influenced by the host factor apolipoprotein E.

Smit TK, Wang B, Ng T, Osborne R, Brew B, Saksena NK. Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants. Virology. 2001;279(2):509–26. doi:10.1006/viro.2000.0681.PubMedCrossRef

Davis LE, Hjelle BL, Miller VE, Palmer DL, Llewellyn AL, Merlin TL, et al. Early viral brain invasion in iatrogenic human immunodeficiency virus infection. Neurology. 1992;42(9):1736–9.PubMedCrossRef

An SF, 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. 1999;58(11):1156–62.PubMedCrossRef

Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R, et al. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS. 1996;10(6):573–85.PubMedCrossRef

Witwer KW, Gama L, Li M, Bartizal CM, Queen SE, Varrone JJ, et al. Coordinated regulation of SIV replication and immune responses in the CNS. PLoS ONE. 2009;4(12):e8129. doi:10.1371/journal.pone.0008129.PubMedCentralPubMedCrossRef

McCarthy M, He J, Wood C. HIV-1 strain-associated variability in infection of primary neuroglia. J Neurovirol. 1998;4(1):80–9.PubMedCrossRef

Lawrence DM, Durham LC, Schwartz L, Seth P, Maric D, Major EO. Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells. J Virol. 2004;78(14):7319–28. doi:10.1128/JVI.78.14.7319-7328.2004.PubMedCentralPubMedCrossRef

Rumbaugh JA, Nath A. Developments in HIV neuropathogenesis. Curr Pharm Des. 2006;12(9):1023–44.PubMedCrossRef

Yao H, Bethel-Brown C, Li CZ, Buch SJ. HIV neuropathogenesis: a tight rope walk of innate immunity. J Neuroimmune Pharmacol. 2010;5(4):489–95. doi:10.1007/s11481-010-9211-1.PubMedCentralPubMedCrossRef

10.

Kaul M. HIV’s double strike at the brain: neuronal toxicity and compromised neurogenesis. Front Biosci. 2008;13:2484–94.PubMedCentralPubMedCrossRef

11.

Lampron A, Elali A, Rivest S. Innate immunity in the CNS: redefining the relationship between the CNS and Its environment. Neuron. 2013;78(2):214–32. doi:10.1016/j.neuron.2013.04.005.PubMedCrossRef

12.

Streit WJ, Kincaid-Colton CA. The brain’s immune system. Sci Am. 1995;273(5):54–5, 8–61.

13.

Perry VH, Hume DA, Gordon S. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience. 1985;15(2):313–26.PubMedCrossRef

14.

Tambuyzer BR, Ponsaerts P, Nouwen EJ. Microglia: gatekeepers of central nervous system immunology. J Leukoc Biol. 2009;85(3):352–70. doi:10.1189/jlb.0608385.PubMedCrossRef

15.

Boche D, Perry VH, Nicoll JA. Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol. 2013;39(1):3–18. doi:10.1111/nan.12011.PubMedCrossRef

16.

Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci USA. 1991;88(16):7438–42.PubMedCentralPubMedCrossRef

17.

Becher B, Antel JP. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia. 1996;18(1):1–10. doi:10.1002/(SICI)1098-1136(199609)18:1<1:AID-GLIA1>3.0.CO;2-6.PubMedCrossRef

18.

Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30(1):16–34. doi:10.3109/08830185.2010.529976.PubMedCrossRef

19.

Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511. doi:10.1038/nri1391.PubMedCrossRef

20.

Gras G, Chretien F, Vallat-Decouvelaere AV, Le Pavec G, Porcheray F, Bossuet C, et al. Regulated expression of sodium-dependent glutamate transporters and synthetase: a neuroprotective role for activated microglia and macrophages in HIV infection? Brain Pathol. 2003;13(2):211–22.PubMedCrossRef

21.

Vallat-Decouvelaere AV, Chretien F, Gras G, Le Pavec G, Dormont D, Gray F. Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia? J Neuropathol Exp Neurol. 2003;62(5):475–85.PubMed

22.

Kaushik DK, Gupta M, Basu A. Microglial response to viral challenges: every silver lining comes with a cloud. Front Biosci (Landmark Ed). 2011;16:2187–205.

23.

Polazzi E, Levi G, Minghetti L. Human immunodeficiency virus type 1 Tat protein stimulates inducible nitric oxide synthase expression and nitric oxide production in microglial cultures. J Neuropathol Exp Neurol. 1999;58(8):825–31.PubMedCrossRef

24.

Olivetta E, Percario Z, Fiorucci G, Mattia G, Schiavoni I, Dennis C, et al. HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: involvement of Nef endocytotic signals and NF-kappa B activation. J Immunol. 2003;170(4):1716–27.PubMedCrossRef

25.

Muthumani K, Choo AY, Premkumar A, Hwang DS, Thieu KP, Desai BM, et al. Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism. Cell Death Differ. 2005;12(Suppl 1):962–70. doi:10.1038/sj.cdd.4401583.PubMedCrossRef

26.

Guo L, Xing Y, Pan R, Jiang M, Gong Z, Lin L, et al. Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis. PLoS One. 2013;8(8):e70565. doi:10.1371/journal.pone.0070565.PubMedCentralPubMedCrossRef

27.

Louboutin JP, Reyes BA, Agrawal L, Van Bockstaele EJ, Strayer DS. HIV-1 gp120-induced neuroinflammation: relationship to neuron loss and protection by rSV40-delivered antioxidant enzymes. Exp Neurol. 2010;221(1):231–45. doi:10.1016/j.expneurol.2009.11.004.PubMedCrossRef

28.

Asensio VC, Maier J, Milner R, Boztug K, Kincaid C, Moulard M, et al. Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytes in vivo and in vitro. J Virol. 2001;75(15):7067–77. doi:10.1128/JVI.75.15.7067-7077.2001.PubMedCentralPubMedCrossRef

29.

Churchill M, Nath A. Where does HIV hide? A focus on the central nervous system. Curr Opin HIV AIDS. 2013;8(3):165–9. doi:10.1097/COH.0b013e32835fc601.PubMedCrossRef

30.

Streit WJ, Mrak RE, Griffin WS. Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004;1(1):14. doi:10.1186/1742-2094-1-14.PubMedCentralPubMedCrossRef

31.

Nedergaard M, Ransom B, Goldman SA. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003;26(10):523–30. doi:10.1016/j.tins.2003.08.008.PubMedCrossRef

32.

Sherwood CC, Stimpson CD, Raghanti MA, Wildman DE, Uddin M, Grossman LI, et al. Evolution of increased glia-neuron ratios in the human frontal cortex. Proc Natl Acad Sci USA. 2006;103(37):13606–11. doi:10.1073/pnas.0605843103.PubMedCentralPubMedCrossRef

33.

Bachoo RM, Kim RS, Ligon KL, Maher EA, Brennan C, Billings N, et al. Molecular diversity of astrocytes with implications for neurological disorders. Proc Natl Acad Sci USA. 2004;101(22):8384–9. doi:10.1073/pnas.0402140101.PubMedCentralPubMedCrossRef

34.

Davies DL, Niesman IR, Boop FA, Phelan KD. Heterogeneity of astroglia cultured from adult human temporal lobe. Int J Dev Neurosci. 2000;18(2–3):151–60.PubMedCrossRef

35.

Chaboub LS, Deneen B. Developmental origins of astrocyte heterogeneity: the final frontier of CNS development. Dev Neurosci. 2012;34(5):379–88. doi:10.1159/000343723.PubMedCentralPubMedCrossRef

36.

Fields RD, Stevens-Graham B. New insights into neuron-glia communication. Science. 2002;298(5593):556–62. doi:10.1126/science.298.5593.556.PubMedCentralPubMedCrossRef

37.

Bezzi P, Volterra A. A neuron-glia signalling network in the active brain. Curr Opin Neurobiol. 2001;11(3):387–94.PubMedCrossRef

38.

Jensen CJ, Massie A, De Keyser J. Immune players in the CNS: the astrocyte. J Neuroimmune Pharmacol. 2013;8(4):824–39. doi:10.1007/s11481-013-9480-6.PubMedCrossRef

39.

Ventura R, Harris KM. Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci. 1999;19(16):6897–906.PubMed

40.

Halassa MM, Fellin T, Haydon PG. The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med. 2007;13(2):54–63. doi:10.1016/j.molmed.2006.12.005.PubMedCrossRef

41.

Brown AM, Ransom BR. Astrocyte glycogen and brain energy metabolism. Glia. 2007;55(12):1263–71. doi:10.1002/glia.20557.PubMedCrossRef

42.

Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest. 2012;122(7):2454–68. doi:10.1172/JCI60842.PubMedCentralPubMedCrossRef

43.

Chung IY, Benveniste EN. Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J Immunol. 1990;144(8):2999–3007.PubMed

44.

Kutsch O, Oh J, Nath A, Benveniste EN. Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol. 2000;74(19):9214–21.PubMedCentralPubMedCrossRef

45.

Song HY, Ryu J, Ju SM, Park LJ, Lee JA, Choi SY, et al. Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kappaB activation in astrocytes. Exp Mol Med. 2007;39(1):27–37. doi:10.1038/emm.2007.4.PubMedCrossRef

46.

Trillo-Pazos G, Diamanturos A, Rislove L, Menza T, Chao W, Belem P, et al. Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection. Brain Pathol. 2003;13(2):144–54.PubMedCrossRef

47.

Shi B, De Girolami U, He J, Wang S, Lorenzo A, Busciglio J, et al. Apoptosis induced by HIV-1 infection of the central nervous system. J Clin Invest. 1996;98(9):1979–90. doi:10.1172/JCI119002.PubMedCentralPubMedCrossRef

48.

Thompson KA, McArthur JC, Wesselingh SL. Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Ann Neurol. 2001;49(6):745–52.PubMedCrossRef

49.

Kim SY, Li J, Bentsman G, Brooks AI, Volsky DJ. Microarray analysis of changes in cellular gene expression induced by productive infection of primary human astrocytes: implications for HAD. J Neuroimmunol. 2004;157(1–2):17–26. doi:10.1016/j.jneuroim.2004.08.032.PubMedCrossRef

50.

Cosenza-Nashat MA, Si Q, Zhao ML, Lee SC. Modulation of astrocyte proliferation by HIV-1: differential effects in productively infected, uninfected, and Nef-expressing cells. J Neuroimmunol. 2006;178(1–2):87–99. doi:10.1016/j.jneuroim.2006.05.020.PubMedCrossRef

51.

Galey D, Becker K, Haughey N, Kalehua A, Taub D, Woodward J, et al. Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes. J Neurovirol. 2003;9(3):358–71. doi:10.1080/13550280390201119.PubMedCrossRef

52.

Borjabad A, Brooks AI, Volsky DJ. Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders. J Neuroimmune Pharmacol. 2010;5(1):44–62. doi:10.1007/s11481-009-9167-1.PubMedCentralPubMedCrossRef

53.

Su ZZ, Kang DC, Chen Y, Pekarskaya O, Chao W, Volsky DJ, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 2002;21(22):3592–602. doi:10.1038/sj.onc.1205445.PubMedCrossRef

54.

Li J, Bentsman G, Potash MJ, Volsky DJ. Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection. BMC Neurosci. 2007;8:31. doi:10.1186/1471-2202-8-31.PubMedCentralPubMedCrossRef

55.

Benos DJ, Hahn BH, Bubien JK, Ghosh SK, Mashburn NA, Chaikin MA, et al. Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transport in astrocytes: implications for AIDS dementia complex. Proc Natl Acad Sci USA. 1994;91(2):494–8.PubMedCentralPubMedCrossRef

56.

Wang Z, Pekarskaya O, Bencheikh M, Chao W, Gelbard HA, Ghorpade A, et al. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology. 2003;312(1):60–73.PubMedCrossRef

57.

Prehaud C, Megret F, Lafage M, Lafon M. Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J Virol. 2005;79(20):12893–904. doi:10.1128/JVI.79.20.12893-12904.2005.PubMedCentralPubMedCrossRef

58.

Wekerle H. Planting and pruning in the brain: MHC antigens involved in synaptic plasticity? Proc Natl Acad Sci USA. 2005;102(1):3–4. doi:10.1073/pnas.0408495101.PubMedCentralPubMedCrossRef

59.

Neumann H, Schmidt H, Cavalie A, Jenne D, Wekerle H. Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. J Exp Med. 1997;185(2):305–16.PubMedCentralPubMedCrossRef

60.

Redwine JM, Buchmeier MJ, Evans CF. In vivo expression of major histocompatibility complex molecules on oligodendrocytes and neurons during viral infection. Am J Pathol. 2001;159(4):1219–24. doi:10.1016/S0002-9440(10)62507-2.PubMedCentralPubMedCrossRef

61.

Petito CK, Torres-Munoz JE, Zielger F, McCarthy M. Brain CD8⁺ and cytotoxic T lymphocytes are associated with, and may be specific for, human immunodeficiency virus type 1 encephalitis in patients with acquired immunodeficiency syndrome. J Neurovirol. 2006;12(4):272–83. doi:10.1080/13550280600879204.PubMedCrossRef

62.

Chakraborty S, Nazmi A, Dutta K, Basu A. Neurons under viral attack: victims or warriors? Neurochem Int. 2010;56(6–7):727–35. doi:10.1016/j.neuint.2010.02.016.PubMedCrossRef

63.

Bu G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci. 2009;10(5):333–44. doi:10.1038/nrn2620.PubMedCentralPubMedCrossRef

64.

Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr. 2000;71(2):621S–9S.PubMed

65.

Kuhlmann I, Minihane AM, Huebbe P, Nebel A, Rimbach G. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review. Lipids Health Dis. 2010;9:8. doi:10.1186/1476-511X-9-8.PubMedCentralPubMedCrossRef

66.

Egensperger R, Kosel S, von Eitzen U, Graeber MB. Microglial activation in Alzheimer disease: association with APOE genotype. Brain Pathol. 1998;8(3):439–47.PubMedCrossRef

67.

Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2000;1:507–37.PubMedCrossRef

68.

Han X. The role of apolipoprotein E in lipid metabolism in the central nervous system. Cell Mol Life Sci. 2004;61(15):1896–906. doi:10.1007/s00018-004-4009-z.PubMedCrossRef

69.

Gee JR, Keller JN. Astrocytes: regulation of brain homeostasis via apolipoprotein E. Int J Biochem Cell Biol. 2005;37(6):1145–50. doi:10.1016/j.biocel.2004.10.004.PubMedCrossRef

70.

Hatters DM, Peters-Libeu CA, Weisgraber KH. Apolipoprotein E structure: insights into function. Trends Biochem Sci. 2006;31(8):445–54. doi:10.1016/j.tibs.2006.06.008.PubMedCrossRef

71.

Qiu Z, Hyman BT, Rebeck GW. Apolipoprotein E receptors mediate neurite outgrowth through activation of p44/42 mitogen-activated protein kinase in primary neurons. J Biol Chem. 2004;279(33):34948–56. doi:10.1074/jbc.M401055200.PubMedCrossRef

72.

Yamamoto T, Choi HW, Ryan RO. Apolipoprotein E isoform-specific binding to the low-density lipoprotein receptor. Anal Biochem. 2008;372(2):222–6. doi:10.1016/j.ab.2007.09.005.PubMedCentralPubMedCrossRef

73.

Gregg RE, Zech LA, Schaefer EJ, Stark D, Wilson D, Brewer HB Jr. Abnormal in vivo metabolism of apolipoprotein E4 in humans. J Clin Invest. 1986;78(3):815–21. doi:10.1172/JCI112645.PubMedCentralPubMedCrossRef

74.

Weisgraber KH. Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J Lipid Res. 1990;31(8):1503–11.PubMed

75.

Weisgraber KH. Apolipoprotein E structure-function relationships. Adv Protein Chem. 1994;45:249–302.PubMedCrossRef

76.

Hauser PS, Narayanaswami V, Ryan RO. Apolipoprotein E from lipid transport to neurobiology. Prog Lipid Res. 2011;50(1):62–74. doi:10.1016/j.plipres.2010.09.001.PubMedCentralPubMedCrossRef

77.

DeMattos RB, Rudel LL, Williams DL. Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth. J Lipid Res. 2001;42(6):976–87.PubMed

78.

Bellosta S, Nathan BP, Orth M, Dong LM, Mahley RW, Pitas RE. Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth. J Biol Chem. 1995;270(45):27063–71.PubMedCrossRef

79.

Nathan BP, Jiang Y, Wong GK, Shen F, Brewer GJ, Struble RG. Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein. Brain Res. 2002;928(1–2):96–105.PubMedCrossRef

80.

DeMattos RB, Curtiss LK, Williams DL. A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins. J Biol Chem. 1998;273(7):4206–12.PubMedCrossRef

81.

Fagan AM, Bu G, Sun Y, Daugherty A, Holtzman DM. Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein. J Biol Chem. 1996;271(47):30121–5.PubMedCrossRef

82.

Frank A, Diez-Tejedor E, Bullido MJ, Valdivieso F, Barreiro P. APOE genotype in cerebrovascular disease and vascular dementia. J Neurol Sci. 2002;203–204:173–6.PubMedCrossRef

83.

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123):921–3.PubMedCrossRef

84.

Corder EH, Robertson K, Lannfelt L, Bogdanovic N, Eggertsen G, Wilkins J, et al. HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy. Nat Med. 1998;4(10):1182–4.PubMedCrossRef

85.

Andres MA, Feger U, Nath A, Munsaka S, Jiang CS, Chang L. APOE epsilon4 allele and CSF APOE on cognition in HIV-infected subjects. J Neuroimmune Pharmacol. 2011;6(3):389–98. doi:10.1007/s11481-010-9254-3.

86.

Dunlop O, Goplen AK, Liestol K, Myrvang B, Rootwelt H, Christophersen B, et al. HIV dementia and apolipoprotein E. Acta Neurol Scand. 1997;95(5):315–8.PubMedCrossRef

87.

Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, et al. Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression. Proc Natl Acad Sci USA. 2008;105(25):8718–23.PubMedCentralPubMedCrossRef

88.

de Bont N, Netea MG, Demacker PN, Verschueren I, Kullberg BJ, van Dijk KW, et al. Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. J Lipid Res. 1999;40(4):680–5.PubMed

89.

Roselaar SE, Daugherty A. Apolipoprotein E-deficient mice have impaired innate immune responses to Listeria monocytogenes in vivo. J Lipid Res. 1998;39(9):1740–3.PubMed

90.

Ophir G, Amariglio N, Jacob-Hirsch J, Elkon R, Rechavi G, Michaelson DM. Apolipoprotein E4 enhances brain inflammation by modulation of the NF-kappaB signaling cascade. Neurobiol Dis. 2005;20(3):709–18. doi:10.1016/j.nbd.2005.05.002.PubMedCrossRef

91.

Ophir G, Meilin S, Efrati M, Chapman J, Karussis D, Roses A, et al. Human apoE3 but not apoE4 rescues impaired astrocyte activation in apoE null mice. Neurobiol Dis. 2003;12(1):56–64.PubMedCrossRef

92.

Vitek MP, Brown CM, Colton CA. APOE genotype-specific differences in the innate immune response. Neurobiol Aging. 2009;30(9):1350–60. doi:10.1016/j.neurobiolaging.2007.11.014.PubMedCentralPubMedCrossRef

93.

Maezawa I, Nivison M, Montine KS, Maeda N, Montine TJ. Neurotoxicity from innate immune response is greatest with targeted replacement of E4 allele of apolipoprotein E gene and is mediated by microglial p38MAPK. FASEB J. 2006;20(6):797–9. doi:10.1096/fj.05-5423fje.PubMed

94.

Maezawa I, Maeda N, Montine TJ, Montine KS. Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice. J Neuroinflammation. 2006;3:10. doi:10.1186/1742-2094-3-10.PubMedCentralPubMedCrossRef

95.

McCarthy M, Vidaurre I, Geffin R. Maturing neurons are selectively sensitive to human immunodeficiency virus type 1 exposure in differentiating human neuroepithelial progenitor cell cultures. J Neurovirol. 2006;12(5):333–48. doi:10.1080/13550280600915347.PubMedCrossRef

96.

Martinez R, Chunjing W, Geffin R, McCarthy M. Depressed neurofilament expression associates with apolipoprotein E3/E4 genotype in maturing human fetal neurons exposed to HIV-1. J Neurovirol. 2012;18(4):323–30. doi:10.1007/s13365-012-0079-0.PubMedCrossRef

97.

Geffin R, Martinez R, Perez R, Issac B, McCarthy M. Apolipoprotein E-dependent differences in innate immune responses of maturing human neuroepithelial progenitor cells exposed to HIV-1. J Neuroimmune Pharmacol. 2013;8(4):1010–26. doi:10.1007/s11481-013-9478-0.PubMedCrossRef

98.

Li Q, Smith AJ, Schacker TW, Carlis JV, Duan L, Reilly CS, et al. Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection. J Immunol. 2009;183(3):1975–82. doi:10.4049/jimmunol.0803222.PubMedCentralPubMedCrossRef

99.

Sedaghat AR, German J, Teslovich TM, Cofrancesco J Jr, Jie CC, Talbot CC Jr, et al. Chronic CD4⁺ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol. 2008;82(4):1870–83. doi:10.1128/JVI.02228-07.PubMedCentralPubMedCrossRef

100.

Haller O, Staeheli P, Kochs G. Interferon-induced Mx proteins in antiviral host defense. Biochimie. 2007;89(6–7):812–8. doi:10.1016/j.biochi.2007.04.015.PubMedCrossRef

101.

Okumura A, Lu G, Pitha-Rowe I, Pitha PM. Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15. Proc Natl Acad Sci USA. 2006;103(5):1440–5. doi:10.1073/pnas.0510518103.PubMedCentralPubMedCrossRef

102.

Pincetic A, Kuang Z, Seo EJ, Leis J. The interferon-induced gene ISG15 blocks retrovirus release from cells late in the budding process. J Virol. 2010;84(9):4725–36. doi:10.1128/JVI.02478-09.PubMedCentralPubMedCrossRef

103.

Neil SJ, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008;451(7177):425–30. doi:10.1038/nature06553.PubMedCrossRef

104.

Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC, et al. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell. 2009;139(3):499–511. doi:10.1016/j.cell.2009.08.039.PubMedCentralPubMedCrossRef

105.

McNatt MW, Zang T, Bieniasz PD. Vpu binds directly to tetherin and displaces it from nascent virions. PLoS Pathog. 2013;9(4):e1003299. doi:10.1371/journal.ppat.1003299.PubMedCentralPubMedCrossRef

106.

Lu J, Pan Q, Rong L, He W, Liu SL, Liang C. The IFITM proteins inhibit HIV-1 infection. J Virol. 2011;85(5):2126–37. doi:10.1128/JVI.01531-10.PubMedCentralPubMedCrossRef

107.

Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472(7344):481–5. doi:10.1038/nature09907.PubMedCentralPubMedCrossRef

108.

Chutiwitoonchai N, Hiyoshi M, Hiyoshi-Yoshidomi Y, Hashimoto M, Tokunaga K, Suzu S. Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins. Microbes Infect. 2013;15(4):280–90. doi:10.1016/j.micinf.2012.12.003.PubMedCrossRef

109.

Roberts ES, Zandonatti MA, Watry DD, Madden LJ, Henriksen SJ, Taffe MA, et al. Induction of pathogenic sets of genes in macrophages and neurons in NeuroAIDS. Am J Pathol. 2003;162(6):2041–57. doi:10.1016/S0002-9440(10)64336-2.PubMedCentralPubMedCrossRef

110.

Masliah E, Roberts ES, Langford D, Everall I, Crews L, Adame A, et al. Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. J Neuroimmunol. 2004;157(1–2):163–75. doi:10.1016/j.jneuroim.2004.08.026.PubMedCrossRef

111.

Stephens EB, Jackson M, Cui L, Pacyniak E, Choudhuri R, Liverman CS, et al. Early dysregulation of cripto-1 and immunomodulatory genes in the cerebral cortex in a macaque model of neuroAIDS. Neurosci Lett. 2006;410(2):94–9. doi:10.1016/j.neulet.2006.07.066.PubMedCrossRef

112.

Borjabad A, Morgello S, Chao W, Kim SY, Brooks AI, Murray J, et al. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders. PLoS Pathog. 2011;7(9):e1002213. doi:10.1371/journal.ppat.1002213.PubMedCentralPubMedCrossRef

113.

Winkler JM, Chaudhuri AD, Fox HS. Translating the brain transcriptome in neuroAIDS: from non-human primates to humans. J Neuroimmune Pharmacol. 2012;7(2):372–9. doi:10.1007/s11481-012-9344-5.PubMedCentralPubMedCrossRef

Title: Innate immune responses to HIV infection in the central nervous system
Authors: Rebeca Geffin
Micheline McCarthy
Publication date: 01-12-2013
Publisher: Springer US
Published in: Immunologic Research / Issue 1-3/2013
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-013-8445-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Innate immune responses to HIV infection in the central nervous system

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1-3/2013

Secreted heat shock protein gp96-Ig: next-generation vaccines for cancer and infectious diseases

CD30: from basic research to cancer therapy

The immune system and head and neck squamous cell carcinoma: from carcinogenesis to new therapeutic opportunities

Molecular studies and therapeutic targeting of Kaposi’s sarcoma herpesvirus (KSHV/HHV-8) oncogenesis

Neonatal immunology: responses to pathogenic microorganisms and epigenetics reveal an “immunodiverse” developmental state

The IL-2/IL-2R system: from basic science to therapeutic applications to enhance immune regulation