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Journal of NeuroVirology

Erschienen in:

01.06.2015

HIV-1 target cells in the CNS

verfasst von: Sarah B. Joseph, Kathryn T. Arrildt, Christa B. Sturdevant, Ronald Swanstrom

Erschienen in: Journal of NeuroVirology | Ausgabe 3/2015

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Abstract

HIV-1 replication in the central nervous system (CNS) is typically limited by the availability of target cells. HIV-1 variants that are transmitted and dominate the early stages of infection almost exclusively use the CCR5 coreceptor and are well adapted to entering, and thus infecting, cells expressing high CD4 densities similar to those found on CD4+ T cells. While the “immune privileged” CNS is largely devoid of CD4+ T cells, macrophage and microglia are abundant throughout the CNS. These cells likely express CD4 densities that are too low to facilitate efficient entry or allow sustained replication by most HIV-1 isolates. Examination of CNS viral populations reveals that late in disease the CNS of some individuals contains HIV-1 lineages that have evolved the ability to enter cells expressing low levels of CD4 and are well-adapted to entering macrophages. These macrophage-tropic (M-tropic) viruses are able to maintain sustained replication in the CNS for many generations, and their presence is associated with severe neurocognitive impairment. Whether conditions such as pleocytosis are necessary for macrophage-tropic viruses to emerge in the CNS is unknown, and extensive examinations of macrophage-tropic variants have not revealed a genetic signature of this phenotype. It is clear, however, that macrophage tropism is rare among HIV-1 isolates and is not transmitted, but is important due to its pathogenic effects on hosts. Prior to the evolution of macrophage-tropic variants, the viruses that are predominately infecting T cells (R5 T cell-tropic) may infect macrophages at a low level and inefficiently, but this could contribute to the reservoir.

Albright AV, Shieh JTC, O’Connor MJ, Gonzalez-Scarano F (2000) Characterization of cultured microglia that can be infected by HIV-1. J Neurovirology 6:S53–S60

Alexander M, Lynch R, Mulenga J, Allen S, Derdeyn CA, Hunter E (2010) Donor and recipient envs from heterosexual human immunodeficiency virus subtype C transmission pairs require high receptor levels for entry. J Virol 84:4100–4104PubMedCentralPubMed

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMed

Archin NM, Margolis DM (2014) Emerging strategies to deplete the HIV reservoir. Curr Opin Infect Dis 27:29–35PubMedCentralPubMed

Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM (2012) Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487:482–U1650PubMedCentralPubMed

Arima Y, Harada M, Kamimura D, Park JH, Kawano F, Yull FE, Kawamoto T, Iwakura Y, Betz UAK, Marquez G, Blackwell TS, Ohira Y, Hirano T, Murakami M (2012) Regional neural activation defines a gateway for autoreactive T cells to cross the blood–brain barrier. Cell 148:447–457PubMed

Arrildt K, Joseph SB, Swanstrom R (2012) The HIV-1 ENV protein: a coat of many colors. Curr HIV/AIDS Rep 9:52–63

Bagasra O, Lavi E, Bobroski L, Khalili K, Pestaner JP, Tawadros R, Pomerantz RJ (1996) Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: Identification by the combination of in situ polymerase chain reaction and immunohistochemistry. Aids 10:573–585

Berger EA, Murphy PM, Farber JM (1999) Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17:657–700PubMed

Brenchley JM, Hill BJ, Ambrozak DR, Price DA, Guenaga FJ, Casazza JP, Kuruppu J, Yazdani J, Migueles SA, Connors M, Roederer M, Douek DC, Koup RA (2004) T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol 78:1160–1168PubMedCentralPubMed

Brinchmann JE, Albert J, Vartdal F (1991) Few infected CD4+ T cells but a high proportion of replication-competent provirus copies in asymptomatic human immunodeficiency virus type 1 infection. J Virol 65:2019–2023PubMedCentralPubMed

Brown PD, Davies SL, Seake T, Millar ID (2004) Molecular mechanisms of cerebrospinal fluid production. Neuroscience 129:957–970PubMedCentralPubMed

Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function. Journal of Neuroscience 28:264–278

Carrithers MD, Visintin I, Viret C, Janeway CA (2002) Role of genetic background in P selectin-dependent immune surveillance of the central nervous system. J Neuroimmunol 129:51–57PubMed

Cashin K, Roche M, Sterjovski J, Ellett A, Gray LR, Cunningham AL, Ramsland PA, Churchill MJ, Gorry PR (2011) Alternative coreceptor requirements for efficient CCR5- and CXCR4-mediated HIV-1 entry into macrophages. J Virol 85:10699–709PubMedCentralPubMed

Cherner M, Masliah E, Ellis RJ, Marcotte TD, Moore DJ, Grant I, Heaton RK (2002) Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology 59:1563–1567PubMed

Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JAM, Baseler M, Lloyd AL, Nowak MA, Fauci AS (1997) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94:13193–13197PubMedCentralPubMed

Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, Joung J, Foo LC, Thompson A, Chen CF, Smith SJ, Barres BA (2013) Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504:394–400

Churchill MJ, Gorry PR, Cowley D, Lal L, Sonza S, Purcell DFJ, Thompson KA, Gabuzda D, McArthur JC, Pardo CA, Wesselingh SL (2006) Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J Neurovirol 12:146–152PubMed

Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ, Gorry PR (2009) Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol 66:253–258PubMed

Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR (1997) Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185:621–628PubMedCentralPubMed

Cosenza MA, Zhao ML, Si QS, Lee SC (2002) Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol 12:442–455PubMed

Del Bigio MR (2010) Ependymal cells: biology and pathology. Acta Neuropathol 119:55–73PubMed

deVries HE, BlomRoosemalen MCM, vanOosten M, deBoer AG, vanBerkel TJC, Breimer DD, Kuiper J (1996) The influence of cytokines on the integrity of the blood–brain barrier in vitro. J Neuroimmunol 64:37–43

Diamond TL, Roshal M, Jamburuthugoda VK, Reynolds HM, Merriam AR, Lee KY, Balakrishnan M, Bambara RA, Planelles V, Dewhurst S, Kim B (2004) Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem 279:51545–51553PubMedCentralPubMed

Dick AD, Pell M, Brew BJ, Foulcher E, Sedgwick JD (1997) Direct ex vivo flow cytometric analysis of human microglial cell CD4 expression: examination of central nervous system biopsy specimens from HIV-seropositive patients and patients with other neurological disease. AIDS 11:1699–1708PubMed

Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, Casazza JP, Kuruppu J, Kuntsman K, Wolinsky S, Grossman Z, Dybul M, Oxenius A, Price DA, Connors M, Koup RA (2002) HIV preferentially infects HIV-specific CD4(+) T cells. Nature 417:95–98PubMed

Duenas-Decamp MJ, Peters P, Burton D, Clapham PR (2008) Natural resistance of human immunodeficiency virus type 1 to the CD4bs antibody b12 conferred by a glycan and an arginine residue close to the CD4 binding loop. J Virol 82:5807–5814PubMedCentralPubMed

Duenas-Decamp MJ, Peters PJ, Burton D, Clapham PR (2009) Determinants flanking the CD4 binding loop modulate macrophage tropism of human immunodeficiency virus type 1 R5 envelopes. J Virol 83:2575–2583PubMedCentralPubMed

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

Dunfee RL, Thomas ER, Wang JB, Kunstman K, Wolinsky SM, Gabuzda D (2007) Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia. Virology 367:222–234PubMedCentralPubMed

Fabriek BO, Van Haastert ES, Galea I, Polfliet MMJ, Dopp ED, Van den Heuvel MM, Van den Berg TK, De Groot CJA, Van der Valk P, Dijkstra CD (2005) CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 51:297–305PubMed

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

Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295–1300PubMed

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 Neurovirol 7:528–541PubMed

Fulcher JA, Hwangbo Y, Zioni R, Nickle D, Lin XD, Heath L, Mullins JI, Corey L, Zhu TF (2004) Compartmentalization of human immunodeficiency virus type 1 between blood monocytes and CD4(+) T cells during infection. J Virol 78:7883–7893PubMedCentralPubMed

Galea I, Palin K, Newman TA, Van Rooijen N, Perry VH, Boche D (2005) Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain. Glia 49:375–384PubMed

Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18PubMed

Goodenow MM, Collman RG (2006) HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes. J Leukocyte Biol 80:965–972PubMed

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 75:10073–10089PubMedCentralPubMed

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 76:6277–6292PubMedCentralPubMed

Gorry PR, Ong C, Thorpe J, Bannwarth S, Thompson KA, Gatignol A, Wesselingh SL, Purcell DFJ (2003) Astrocyte infection by HIV-1: mechanisms of restricted virus replication, and role in the pathogenesis of HIV-1-associated dementia. Curr HIV Res 1:463–473PubMed

Harouse JM, Kunsch C, Hartle HT, Laughlin MA, Hoxie JA, Wigdahl B, Gonzalezscarano F (1989) CD4-independent infection of human neural cells by human immunodeficiency virus type 1. J Virol 63:2527–2533PubMedCentralPubMed

Harrington PR, Schnell G, Letendre SL, Ritola K, Robertson K, Hall C, Burch CL, Jabara CB, Moore DT, Ellis RJ, Price RW, Swanstrom R (2009) Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS 23:907–915PubMedCentralPubMed

He J, Crews FT (2008) Increased MCP-1 and microglia in various regions of the human alcoholic brain. Exp Neurol 210:349–358PubMedCentralPubMed

Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126PubMed

Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DIS, Lai J, Blankson JN, Siliciano JD, Siliciano RF (2013) Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155:540–551PubMedCentralPubMed

Hockly E, Richon VM, Woodman B, Smith DL, Zhou XB, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PAS, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 100:2041–2046PubMedCentralPubMed

Horikoshi Y, Sasaki A, Taguchi N, Maeda M, Tsukagoshi H, Sato K, Yamaguchi H (2003) Human GLUT5 immunolabeling is useful for evaluating microglial status in neuropathological study using paraffin sections. Acta Neuropathol 105:157–162PubMed

Ince WL, Harrington PR, Schnell GL, Patel-Chhabra M, Burch CL, Menezes P, Price RW, Eron JJ, Swanstrom RI (2009) Major coexisting human immunodeficiency virus type 1 env gene subpopulations in the peripheral blood are produced by cells with similar turnover rates and show little evidence of genetic compartmentalization. J Virol 83:4068–4080PubMedCentralPubMed

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

Isaacman-Beck J, Hermann EA, Yi YJ, Ratcliffe SJ, Mulenga J, Allen S, Hunter E, Derdeyn CA, Collman RG (2009) Heterosexual transmission of human immunodeficiency virus type 1 subtype C: macrophage tropism, alternative coreceptor use, and the molecular anatomy of CCR5 utilization. J Virol 83:8208–8220PubMedCentralPubMed

Joseph SB, Arrildt KT, Swanstrom AE, Schnell G, Lee B, Hoxie JA, Swanstrom R (2014) Quantification of entry phenotypes of macrophage-tropic HIV-1 across a wide range of CD4 densities. J Virol 88:1858–1869PubMedCentralPubMed

Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun CX, Grayson T, Wang SY, Li H, Wei XP, Jiang CL, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM (2008) Identification and characterisation of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105:7552–7557PubMedCentralPubMed

Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553PubMed

Kitamura O, Takeichi T, Wang EL, Tokunaga I, Ishigami A, S-i K (2010) Microglial and astrocytic changes in the striatum of methamphetamine abusers. Legal Med 12:57–62PubMed

Kivisakk P, Trebst C, Liu Z, Tucky BH, Sorensen TL, Rudick RA, Mack M, Ransohoff RM (2002) T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking. Clin Exp Immunol 129:510–518PubMedCentralPubMed

Kivisakk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, Wu LJ, Baekkevold ES, Lassmann H, Staugaitis SM, Campbell JJ, Ransohoff RM (2003) Human cerebrospinal fluid central memory CD4(+) T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A 100:8389–8394PubMedCentralPubMed

Koot M, Keet IPM, Vos AHV, Degoede REY, Roos MTL, Coutinho RA, Miedema F, Schellekens PTA, Tersmette M (1993) Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 118:681–688PubMed

Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen ISY (1987) Dual infection of the central-nervous-system by AIDS viruses with distinct cellular tropisms. Science 236:819–822PubMed

Lambotte O, Taoufik Y, de Goer MG, Wallon C, Goujard C, Delfraissy JF (2000) Detection of infectious HIV in circulating monocytes from patients on prolonged highly active antiretroviral therapy. J Acquir Immune Defic Syndr 23:114–119PubMed

Lamers SL, Gray RR, Salemi M, Huysentruyt LC, McGrath MS (2011) HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues. Infect Genet Evol 11:31–37PubMedCentralPubMed

Lawn SD, Pisell TL, Hirsch CS, Wu M, Butera ST, Toossi Z (2001) Anatomically compartmentalized human immunodeficiency virus replication in HLA-DR(+) cells and CD14(+) macrophages at the site of pleural tuberculosis coinfection. J Infect Dis 184:1127–1133PubMed

Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW (1999) Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A 96:5215–5220PubMedCentralPubMed

Li S, Juarez J, Alali M, Dwyer D, Collman R, Cunningham A, Naif HM (1999) Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates. J Virol 73:9741–9755PubMedCentralPubMed

Li H, Bar KJ, Wang S, Decker JM, Chen Y, Sun C, Salazar-Gonzalez JF, Salazar MG, Learn GH, Morgan CJ, Schumacher JE, Hraber P, Giorgi EE, Bhattacharya T, Korber BT, Perelson AS, Eron JJ, Cohen MS, Hicks CB, Haynes BF, Markowitz M, Keele BF, Hahn BH, Shaw GM (2010) High multiplicity infection by HIV-1 in men who have sex with men. PLoS Pathog 6:e1000890PubMedCentralPubMed

Liu Y, Liu H, Kim BO, Gattone VH, Li JL, 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 78:4120–4133PubMedCentralPubMed

Maher F, Vannucci SJ, Simpson IA (1994) Glucose transporter proteins in brain. FASEB J 8:1003–1011PubMed

Matsuda K, Brown CR, Foley B, Goeken R, Whitted S, Dang Q, Wu F, Plishka R, Buckler-White A, Hirscha VM (2013) Laser capture microdissection assessment of virus compartmentalization in the central nervous systems of macaques infected with neurovirulent simian immunodeficiency virus. J Virol 87:8896–8908PubMedCentralPubMed

McCarthy M, He J, Wood C (1998) HIV-1 strain-associated variability in infection of primary neuroglia. J Neurovirol 4:80–89PubMed

Mefford ME, Gorry PR, Kunstman K, Wolinsky SM, Gabuzda D (2008) Bioinformatic prediction programs underestimate the frequency of CXCR4 usage by R5X4 HIV type 1 in brain and other tissues. Aids Res Hum Retroviruses 24:1215–1220PubMedCentralPubMed

Musich T, Peters PJ, Duenas-Decamp MJ, Gonzalez-Perez MP, Robinson J, Zolla-Pazner S, Ball JK, Luzuriaga K, Clapham PR (2011) A conserved determinant in the V1 loop of HIV-1 modulates the V3 loop to prime low CD4 use and macrophage infection. J Virol 85:2397–2405PubMedCentralPubMed

Nag S, Begley DJ (2005) Blood–brain barrier, exchange of metabolites and gases. In: Kalimo H (ed) Pathology and genetics: cerebrovascular diseases. Neuropath, Basel, pp 22–29

Naif HM, Li S, Alali M, Sloane A, Wu LJ, Kelly M, Lynch G, Lloyd A, Cunningham AL (1998) CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection. J Virol 72:830–836PubMedCentralPubMed

Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530PubMed

Neuenjacob E, Arendt G, Wendtland B, Jacob B, Schneeweis M, Wechsler W (1993) Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions. Clin Neuropathol 12:315–324

Nuovo GJ, Alfieri ML (1996) AIDS dementia is associated with massive, activated HIV-1 infection and concomitant expression of several cytokines. Mol Med 2:358–366

Nuutinen T, Suuronen T, Kauppinen A, Salminen A (2010) Valproic acid stimulates clusterin expression in human astrocytes: implications for Alzheimer’s disease. Neurosci Lett 475:64–68PubMed

Ochsenbauer C, Edmonds TG, Ding HT, Keele BF, Decker J, Salazar MG, Salazar-Gonzalez JF, Shattock R, Haynes BF, Shaw GM, Hahn BH, Kappes JC (2012) Generation of transmitted/founder HIV-1 infectious molecular clones and characterization of their replication capacity in CD4 T lymphocytes and monocyte-derived macrophages. J Virol 86:2715–2728PubMedCentralPubMed

Ohagen A, Devitt A, Kunstman KJ, Gorry PR, Rose PP, Korber B, Taylor J, Levy R, Murphy RL, Wolinsky SM, Gabuzda D (2003) Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS. J Virol 77:12336–12345PubMedCentralPubMed

Orenstein JM, Fox C, Wahl SM (1997) Macrophages as a source of HIV during opportunistic infections. Science 276:1857–1861PubMed

Ousman SS, Kubes P (2012) Immune surveillance in the central nervous system. Nat Neurosci 15:1096–1101PubMed

Ouyang Y, Liu L, Zhang Y, Yuan L, Liu Z, Yang S, Wei F, Qiao L, Chen D (2014) Discordant patterns of tissue-specific genetic characteristics in the HIV-1 env gene from HIV-associated neurocognitive disorder (HAND) and non-HAND patients. J Neurovirol 20:332–340

Palmieri D, Lockman PR, Thomas FC, Hua E, Herring J, Hargrave E, Johnson M, Flores N, Qian YZ, Vega-Valle E, Taskar KS, Rudraraju V, Mittapalli RK, Gaasch JA, Bohn KA, Thorsheim HR, Liewehr DJ, Davis S, Reilly JF, Walker R, Bronder JL, Feigenbaum L, Steinberg SM, Camphausen K, Meltzer PS, Richon VM, Smith QR, Steeg PS (2009) Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks. Clin Cancer Res 15:6148–6157PubMed

Parrish NF, Wilen CB, Banks LB, Iyer SS, Pfaff JM, Salazar-Gonzalez JF, Salazar MG, Decker JM, Parrish EH, Berg A, Hopper J, Hora B, Kumar A, Mahlokozera T, Yuan S, Coleman C, Vermeulen M, Ding H, Ochsenbauer C, Tilton JC, Permar SR, Kappes JC, Betts MR, Busch MP, Gao F, Montefiori D, Haynes BF, Shaw GM, Hahn BH, Doms RW (2012) Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. PLoS Pathog 8:e1002686PubMedCentralPubMed

Perdiguero EG, Schulz C, Geissmann F (2013) Development and homeostasis of “resident” myeloid cells: the case of the microglia. Glia 61:112–120

Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271:1582–1586PubMed

Perelson AS, Essunger P, Cao YZ, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD (1997) Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387:188–191PubMed

Peters PJ, Bhattacharya J, Hibbitts S, Dittmar MT, Simmons G, Bell J, Simmonds P, Clapham PR (2004) Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages. J Virol 78:6915–6926PubMedCentralPubMed

Peters PJ, Sullivan WM, Duenas-Decamp MJ, Bhattacharya J, Ankghuambom C, Brown R, Luzuriaga K, Bell J, Simmonds P, Ball J, Clapham PR (2006) Non-macrophage-tropic human immunodeficiency virus type 1 R5 envelopes predominate in blood, lymph nodes, and semen: implications for transmission and pathogenesis. J Virol 80:6324–6332PubMedCentralPubMed

Petito CK, Chen HX, 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 Neurovirol 5:670–677PubMed

Pilcher CD, Shugars DC, Fiscus SA, Miller WC, Menezes P, Giner J, Dean B, Robertson K, Hart CE, Lennox JL, Eron JJ Jr, Hicks CB (2001) HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health. AIDS 15:837–45PubMed

Ping LH, Joseph SB, Anderson JA, Abrahams MR, Salazar-Gonzalez JF, Kincer LP, Treurnicht FK, Arney L, Ojeda S, Zhang M, Keys J, Potter EL, Chu H, Moore P, Salazar MG, Iyer S, Jabara C, Kirchherr J, Mapanje C, Ngandu N, Seoighe C, Hoffman I, Gao F, Tang Y, Labranche C, Lee B, Saville A, Vermeulen M, Fiscus S, Morris L, Karim SA, Haynes BF, Shaw GM, Korber BT, Hahn BH, Cohen MS, Montefiori D, Williamson C, Swanstrom R (2013) Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design. J Virol 87:7218–7233PubMedCentralPubMed

Polazzi E, Monti B (2010) Microglia and neuroprotection: from in vitro studies to therapeutic applications. Prog Neurobiol 92:293–315PubMed

Psallidopoulos MC, Schnittman SM, Thompson LM, Baseler M, Fauci AS, Lane HC, Salzman NP (1989) Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. J Virol 63:4626–4631PubMedCentralPubMed

Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262PubMed

Ransohoff RM, Engelhardt B (2012) The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 12:623–635PubMed

Ransohoff RM, Kivisakk P, Kidd G (2003) Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 3:569–81PubMed

Rossi F, Querido B, Nimmagadda M, Cocklin S, Navas-Martin S, Martin-Garcia J (2008) The V1–V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Retrovirology 5:89PubMedCentralPubMed

Salazar-Gonzalez JF, Salazar MG, Keele BF, Learn GH, Giorgi EE, Li H, Decker JM, Wang SY, Baalwa J, Kraus MH, Parrish NF, Shaw KS, Guffey MB, Bar KJ, Davis KL, Ochsenbauer-Jambor C, Kappes JC, Saag MS, Cohen MS, Mulenga J, Derdeyn CA, Allen S, Hunter E, Markowitz M, Hraber P, Perelson AS, Bhattacharya T, Haynes BF, Korber BT, Hahn BH, Shaw GM (2009) Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med 206:1273–1289PubMedCentralPubMed

Salimi H, Roche M, Webb N, Gray LR, Chikere K, Sterjovski J, Ellett A, Wesselingh SL, Ramsland PA, Lee B, Churchill MJ, Gorry PR (2013) Macrophage-tropic HIV-1 variants from brain demonstrate alterations in the way gp120 engages both CD4 and CCR5. J Leukocyte Biol 93:113–126PubMedCentralPubMed

Sasaki A, Yamaguchi H, Horikoshi Y, Tanaka G, Nakazato Y (2004) Expression of glucose transporter 5 by microglia in human gliomas. Neuropathol Appl Neurobiol 30:447–455PubMed

Schnell G, Spudich S, Harrington P, Price RW, Swanstrom R (2009) Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia. PLoS Pathog 5:e1000395PubMedCentralPubMed

Schnell G, Price RW, Swanstrom R, Spudich S (2010) Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J Virol 84:2395–2407PubMedCentralPubMed

Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R (2011) HIV-1 replication in the central nervous system occurs in two distinct cell types. PLoS Pathog 7:e1002286PubMedCentralPubMed

Schnittman SM, Psallidopoulos MC, Lane HC, Thompson L, Baseler M, Massari F, Fox CH, Salzman NP, Fauci AS (1989) The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 245:305–308PubMed

Shirai Y (1921) On the transplantation of the rat sarcoma in adult heterogeneous animals. Jpn Med World 1:14–15

Simon V, Ho DD (2003) HIV-1 dynamics in vivo: implications for therapy. Nat Rev Microbiol 1:181–190PubMed

Sleasman JW, Aleixo LF, Morton A, SkodaSmith S, Goodenow MM (1996) CD4+ memory T cells are the predominant population of HIV-1-infected lymphocytes in neonates and children. AIDS 10:1477–1484PubMed

Sonza S, Maerz A, Uren S, Violo A, Hunter S, Boyle W, Crowe S (1995) Susceptibility of human monocytes to HIV type 1 infection in vitro is not dependent on their level of CD4 expression. Aids Res Hum Retroviruses 11:769–776PubMed

Sonza S, Mutimer HP, Oelrichs R, Jardine D, Harvey K, Dunne A, Purcell DF, Birch C, Crowe SM (2001) Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AIDS 15:17–22PubMed

Spivak AM, Salgado M, Rabi SA, O'Connell KA, Blankson JN (2011) Circulating monocytes are not a major reservoir of HIV-1 in elite suppressors. J Virol 85:10399–403PubMedCentralPubMed

Spudich S, Gisslen M, Hagberg L, Lee E, Liegler T, Brew B, Fuchs D, Tambussi G, Cinque P, Hecht FM, Price RW (2011) Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden. J Infect Dis 204:753–60PubMedCentralPubMed

Stoler MH, Eskin TA, Benn S, Angerer RC, Angerer LM (1986) Human T-cell lymphotropic virus type III infection of the central nervous system. A preliminary in situ analysis. JAMA 256:2360–2364PubMed

Sturdevant CB, Dow A, Jabara CB, Joseph SB, Schnell G, Takamune N, Mallewa M, Heyderman RS, Van Rie A, Swanstrom R (2012) Central nervous system compartmentalization of HIV-1 subtype C variants early and late in infection in young children. PLoS Pathog 8:e1003094PubMedCentralPubMed

Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD (1996) Localization of HIV-1 in human brain using polymerase chain reaction in situ hybridization and immunocytochemistry. Ann Neurol 39:705–711

Tasdemir-Yilmaz OE, Freeman MR (2014) Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Gene Dev 28:20–33

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 360:105–119PubMedCentralPubMed

Thompson KA, Churchill MJ, Gorry PR, Sterjovski J, Oelrichs RB, Wesselingh SL, McLean CA (2004) Astrocyte specific viral strains in HIV dementia. Ann Neurol 56:873–877PubMed

Toma J, Whitcomb JM, Petropoulos CJ, Huang W (2010) Dual-tropic HIV type 1 isolates vary dramatically in their utilization of CCR5 and CXCR4 coreceptors. Aids 24:2181–2186PubMed

Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A (2011) The role of microglia in the healthy brain. J Neurosci 31:16064–16069PubMed

Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J (2012) Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 206:275–282PubMedCentralPubMed

Vannucci SJ, Maher F, Simpson IA (1997) Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 21:2–21PubMed

Verkhratsky A, Orkand RK, Kettenmann H (1998) Glial calcium: homeostasis and signaling function. Physiol Rev 78:99–141PubMed

Wang JB, Crawford K, Yuan ML, Wang H, Gorry PR, Gabuzda D (2002) Regulation of CC chemokine receptor 5 and CD4 expression and human immunodeficiency virus type 1 replication in human macrophages and microglia by T helper type 2 cytokines. J Infect Dis 185:885–897PubMed

Wang T, Xu YN, Zhu HY, Andrus T, Ivanov SB, Pan C, Dolores J, Dann GC, Zhou M, Forte D, Yang ZH, Holte S, Corey L, Zhu TF (2013) Successful isolation of infectious and high titer human monocyte-derived HIV-1 from two subjects with discontinued therapy. Plos One 8:e65071PubMedCentralPubMed

Warren KE, McCully C, Dvinge H, Tjornelund J, Sehested M, Lichenstein HS, Balis FM (2008) Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates. Cancer Chemother Pharmacol 62:433–437PubMed

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

Wei XP, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117–122PubMed

Wightman F, Ellenberg P, Churchill M, Lewin SR (2012) HDAC inhibitors in HIV. Immunol Cell Biol 90:47–54PubMed

Wilen CB, Parrish NF, Pfaff JM, Decker JM, Henning EA, Haim H, Petersen JE, Wojcechowskyj JA, Sodroski J, Haynes BF, Montefiori DC, Tilton JC, Shaw GM, Hahn BH, Doms RW (2011) Phenotypic and immunologic comparison of clade B transmitted/founder and chronic HIV-1 envelope glycoproteins. J Virol 85:8514–8527PubMedCentralPubMed

Wilen CB, Tilton JC, Doms RW (2012) HIV: Cell binding and Entry. In: Bushman FD, Nabel GJ, Swanstrom R (eds) HIV: from biology to prevention to treatment. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MBA (1986) Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A 83:7089–7093PubMedCentralPubMed

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 193:905–915PubMedCentralPubMed

Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD (1997) Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278:1291–1295PubMed

Xu YN, Zhu HY, Wilcox CK, van't Wout A, Andrus T, Llewellyn N, Stamatatos L, Mullins JI, Corey L, Zhu TF (2008) Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus. J Infect Dis 197:309–318PubMed

Yi YJ, Chen W, Frank I, Cutilli J, Singh A, Starr-Spires L, Sulcove J, Kolson DL, Collman RG (2003) An unusual syncytia-inducing human immunodeficiency virus type 1 primary isolate from the central nervous system that is restricted to CXCR4, replicates efficiently in macrophages, and induces neuronal apoptosis. J Neurovirol 9:432–441PubMed

Yukl SA, Shergill AK, Ho T, Killian M, Girling V, Epling L, Li PL, Wong LK, Crouch P, Deeks SG, Havlir DV, McQuaid K, Sinclair E, Wong JK (2013) The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J Infect Dis 208:1212–1220PubMedCentralPubMed

Zamarchi R, Allavena P, Borsetti A, Stievano L, Tosello V, Marcato N, Esposito G, Roni V, Paganin C, Bianchi G, Titti F, Verani P, Gerosa G, Amadori A (2002) Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes. Clin Exp Immunol 127:321–330PubMedCentralPubMed

Zhou L, Ng T, Yuksel A, Wang B, Dwyer DE, Saksena NK (2008) Absence of HIV infection in the choroid plexus of two patients who died rapidly with HIV-associated dementia. Aids Res Hum Retroviruses 24:839–843PubMed

Zhu TF, Muthui D, Holte S, Nickle D, Feng F, Brodie S, Hwangbo Y, Mullins JI, Corey L (2002) Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 76:707–716PubMedCentralPubMed

Titel: HIV-1 target cells in the CNS
verfasst von: Sarah B. Joseph
Kathryn T. Arrildt
Christa B. Sturdevant
Ronald Swanstrom
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Journal of NeuroVirology / Ausgabe 3/2015
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-014-0287-x

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