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Cell–cell contact viral transfer contributes to HIV infection and persistence in astrocytes

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Abstract

Astrocytes are the most abundant cells in the central nervous system and play important roles in human immunodeficiency virus (HIV)/neuro-acquired immunodeficiency syndrome. Detection of HIV proviral DNA, RNA, and early gene products but not late structural gene products in astrocytes in vivo and in vitro indicates that astrocytes are susceptible to HIV infection albeit in a restricted manner. We as well as others have shown that cell-free HIV is capable of entering CD4− astrocytes through human mannose receptor-mediated endocytosis. In this study, we took advantage of several newly developed fluorescence protein-based HIV reporter viruses and further characterized HIV interaction with astrocytes. First, we found that HIV was successfully transferred to astrocytes from HIV-infected CD4+ T cells in a cell–cell contact- and gp120-dependent manner. In addition, we demonstrated that, compared to endocytosis-mediated cell-free HIV entry and subsequent degradation of endocytosed virions, the cell–cell contact between astrocytes and HIV-infected CD4+ T cells led to robust HIV infection of astrocytes but retained the restricted nature of viral gene expression. Furthermore, we showed that HIV latency was established in astrocytes. Lastly, we demonstrated that infectious progeny HIV was readily recovered from HIV latent astrocytes in a cell–cell contact-mediated manner. Taken together, our studies point to the importance of the cell–cell contact-mediated HIV interaction with astrocytes and provide direct evidence to support the notion that astrocytes are HIV latent reservoirs in the central nervous system.

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References

  • Abela IA, Berlinger L, Schanz M, Reynell L, Gunthard HF, Rusert P, Trkola A (2012) Cell–cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies. PLoS Pathog 8:e1002634

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Alexaki A, Quiterio SJ, Liu Y, Irish B, Kilareski E, Nonnemacher MR, Wigdahl B (2007) PMA-induced differentiation of a bone marrow progenitor cell line activates HIV-1 LTR-driven transcription. DNA Cell Biol 26:387–394

    CAS  PubMed  Google Scholar 

  • Aquaro S, Calio R, Balzarini J, Bellocchi MC, Garaci E, Perno CF (2002) Macrophages and HIV infection: therapeutical approaches toward this strategic virus reservoir. Antiviral Res 55:209–225

    CAS  PubMed  Google Scholar 

  • Blanco J, Bosch B, Fernandez-Figueras MT, Barretina J, Clotet B, Este JA (2004) High level of coreceptor-independent HIV transfer induced by contacts between primary CD4 T cells. J Biol Chem 279:51305–51314

    CAS  PubMed  Google Scholar 

  • Bosch B, Grigorov B, Senserrich J, Clotet B, Darlix JL, Muriaux D, Este JA (2008) A clathrin-dynamin-dependent endocytic pathway for the uptake of HIV-1 by direct T cell-T cell transmission. Antiviral Res 80:185–193

    CAS  PubMed  Google Scholar 

  • Brooks DG, Arlen PA, Gao L, Kitchen CM, Zack JA (2003) Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc Natl Acad Sci U S A 100:12955–12960

    CAS  PubMed Central  PubMed  Google Scholar 

  • Canki M, Thai JN, Chao W, Ghorpade A, Potash MJ, Volsky DJ (2001) Highly productive infection with pseudotyped human immunodeficiency virus type 1 (HIV-1) indicates no intracellular restrictions to HIV-1 replication in primary human astrocytes. J Virol 75:7925–7933

    CAS  PubMed Central  PubMed  Google Scholar 

  • Capparelli EV, Letendre SL, Ellis RJ, Patel P, Holland D, McCutchan JA (2005) Population pharmacokinetics of abacavir in plasma and cerebrospinal fluid. Antimicrob Agents Chemother 49:2504–2506

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carroll-Anzinger D, Kumar A, Adarichev V, Kashanchi F, Al-Harthi L (2007) Human immunodeficiency virus-restricted replication in astrocytes and the ability of gamma interferon to modulate this restriction are regulated by a downstream effector of the Wnt signaling pathway. J Virol 81:5864–5871

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen P, Hubner W, Spinelli MA, Chen BK (2007) Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses. J Virol 81:12582–12595

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen P, Chen BK, Mosoian A, Hays T, Ross MJ, Klotman PE, Klotman ME (2011) Virological synapses allow HIV-1 uptake and gene expression in renal tubular epithelial cells. J Am Soc Nephrol 22:496–507

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng-Mayer C, Rutka JT, Rosenblum ML, McHugh T, Stites DP, Levy JA (1987) Human immunodeficiency virus can productively infect cultured human glial cells. Proc Natl Acad Sci U S A 84:3526–3530

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chiodi F, Fuerstenberg S, Gidlund M, Asjo B, Fenyo EM (1987) Infection of brain-derived cells with the human immunodeficiency virus. J Virol 61:1244–1247

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chun TW, Fauci AS (2012) HIV reservoirs: pathogenesis and obstacles to viral eradication and cure. AIDS 26:1261–1268

    PubMed  Google Scholar 

  • Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS (1998) Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J Exp Med 188:83–91

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 66:253–258

    PubMed  Google Scholar 

  • Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, Baltimore D (1999) The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10:661–671

    CAS  PubMed  Google Scholar 

  • Cysique LA, Maruff P, Brew BJ (2004) Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 10:350–357

    PubMed  Google Scholar 

  • Dahabieh MS, Ooms M, Simon V, Sadowski I (2013) A doubly fluorescent HIV-1 reporter shows that the majority of integrated HIV-1 is latent shortly after infection. J Virol 87:4716–4727

    CAS  PubMed Central  PubMed  Google Scholar 

  • Deiva K, Khiati A, Hery C, Salim H, Leclerc P, Horellou P, Tardieu M (2006) CCR5-, DC-SIGN-dependent endocytosis and delayed reverse transcription after human immunodeficiency virus type 1 infection in human astrocytes. AIDS Res Hum Retrovir 22:1152–1161

    CAS  PubMed  Google Scholar 

  • Deslee G, Charbonnier AS, Hammad H, Angyalosi G, Tillie-Leblond I, Mantovani A, Tonnel AB, Pestel J (2002) Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells. J Allergy Clin Immunol 110:763–770

    CAS  PubMed  Google Scholar 

  • Desplats P, Dumaop W, Smith D, Adame A, Everall I, Letendre S, Ellis R, Cherner M, Grant I, Masliah E (2013) Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology 80:1415–1423

    CAS  PubMed Central  PubMed  Google Scholar 

  • Devadas K, Hardegen NJ, Wahl LM, Hewlett IK, Clouse KA, Yamada KM, Dhawan S (2004) Mechanisms for macrophage-mediated HIV-1 induction. J Immunol 173:6735–6744

    CAS  PubMed  Google Scholar 

  • Dewhurst S, Sakai KXHZ, Wasiak A, Volsky DJ (1988) Establishment of human glial cell lines chronically infected with the human immunodeficiency virus. Virology 162:151–159

    CAS  PubMed  Google Scholar 

  • Emiliani S, Van Lint C, Fischle W, Paras P Jr, Ott M, Brady J, Verdin E (1996) A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency. Proc Natl Acad Sci U S A 93:6377–6381

    CAS  PubMed Central  PubMed  Google Scholar 

  • Emiliani S, Fischle W, Ott M, Van Lint C, Amella CA, Verdin E (1998) Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. J Virol 72:1666–1670

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fais S, Capobianchi MR, Abbate I, Castilletti C, Gentile M, Cordiali Fei P, Ameglio F, Dianzani F (1995) Unidirectional budding of HIV-1 at the site of cell-to-cell contact is associated with co-polarization of intercellular adhesion molecules and HIV-1 viral matrix protein. AIDS 9:329–335

    CAS  PubMed  Google Scholar 

  • Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW Jr, Bavari S, Lowekamp BC, Bliss D, Lifson JD, Subramaniam S (2010) 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells. Proc Natl Acad Sci U S A 107:13336–13341

    CAS  PubMed Central  PubMed  Google Scholar 

  • Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5:512–517

    CAS  PubMed  Google Scholar 

  • Goldenthal KL, Pastan I, Willingham MC (1984) Initial steps in receptor-mediated endocytosis. The influence of temperature on the shape and distribution of plasma membrane clathrin-coated pits in cultured mammalian cells. Exp Cell Res 152:558–564

    CAS  PubMed  Google Scholar 

  • Gorry P, Purcell D, Howard J, McPhee D (1998) Restricted HIV-1 infection of human astrocytes: potential role of nef in the regulation of virus replication. J Neurovirol 4:377–386

    CAS  PubMed  Google Scholar 

  • Gorry PR, Howard JL, Churchill MJ, Anderson JL, Cunningham A, Adrian D, McPhee DA, Purcell DF (1999) Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev. J Virol 73:352–361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta P, Balachandran R, Ho M, Enrico A, Rinaldo C (1989) Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody. J Virol 63:2361–2365

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haller C, Fackler OT (2008) HIV-1 at the immunological and T-lymphocytic virological synapse. Biol Chem 389:1253–1260

    CAS  PubMed  Google Scholar 

  • Hao HN, Lyman WD (1999) HIV infection of fetal human astrocytes: the potential role of a receptor-mediated endocytic pathway. Brain Res 823:24–32

    CAS  PubMed  Google Scholar 

  • Hao HN, Chiu FC, Losev L, Weidenheim KM, Rashbaum WK, Lyman WD (1997) HIV infection of human fetal neural cells is mediated by gp120 binding to a cell membrane-associated molecule that is not CD4 nor galactocerebroside. Brain Res 764:149–157

    CAS  PubMed  Google Scholar 

  • Harada S, Koyanagi Y, Yamamoto N (1985) Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science 229:563–566

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hatch WC, Tanaka KE, Calvelli T, Rashbaum WK, Kress Y, Lyman WD (1992) Persistent productive HIV-1 infection of a CD4- human fetal thymocyte line. J Immunol 148:3055–3061

    CAS  PubMed  Google Scholar 

  • Hubner W, McNerney GP, Chen P, Dale BM, Gordon RE, Chuang FY, Li XD, Asmuth DM, Huser T, Chen BK (2009) Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science 323:1743–1747

    PubMed Central  PubMed  Google Scholar 

  • Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN, Griffiths GM, Tanaka Y, Osame M, Bangham CR (2003) Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299:1713–1716

    CAS  PubMed  Google Scholar 

  • Jeeninga RE, Hoogenkamp M, Armand-Ugon M, de Baar M, Verhoef K, Berkhout B (2000) Functional differences between the long terminal repeat transcriptional promoters of human immunodeficiency virus type 1 subtypes A through G. J Virol 74:3740–3751

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jolly C, Kashefi K, Hollinshead M, Sattentau QJ (2004) HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 199:283–293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jolly C, Welsch S, Michor S, Sattentau QJ (2011) The regulated secretory pathway in CD4(+) T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse. PLoS Pathog 7:e1002226

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kandanearatchi A, Williams B, Everall IP (2003) Assessing the efficacy of highly active antiretroviral therapy in the brain. Brain Pathol 13:104–110

    PubMed  Google Scholar 

  • Klaver B, Berkhout B (1994) Comparison of 5’ and 3’ long terminal repeat promoter function in human immunodeficiency virus. J Virol 68:3830–3840

    CAS  PubMed Central  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Langford TD, Letendre SL, Larrea GJ, Masliah E (2003) Changing patterns in the neuropathogenesis of HIV during the HAART era. Brain Pathol 13:195–210

    CAS  PubMed  Google Scholar 

  • Lawson LJ, Perry VH, Gordon S (1992) Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48:405–415

    CAS  PubMed  Google Scholar 

  • Li J, Liu Y, Park IW, He JJ (2002) Expression of exogenous Sam68, the 68-kilodalton SRC-associated protein in mitosis, is able to alleviate impaired Rev function in astrocytes. J Virol 76:4526–4535

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu Y, Li J, Kim BO, Pace BS, He JJ (2002) HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110. J Biol Chem 277:23854–23863

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lokensgard JR, Gekker G, Ehrlich LC, Hu S, Chao CC, Peterson PK (1997) Proinflammatory cytokines inhibit HIV-1 (SF162) expression in acutely infected human brain cell cultures. J Immunol 158:2449–2455

    CAS  PubMed  Google Scholar 

  • Lopez-Herrera A, Liu Y, Rugeles MT, He JJ (2005) HIV-1 interaction with human mannose receptor (hMR) induces production of matrix metalloproteinase 2 (MMP-2) through hMR-mediated intracellular signaling in astrocytes. Biochim Biophys Acta 1741:55–64

    CAS  PubMed  Google Scholar 

  • Luster AD (1998) Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445

    CAS  PubMed  Google Scholar 

  • Malim MH, Cullen BR (1991) HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. Cell 65:241–248

    CAS  PubMed  Google Scholar 

  • Marsh M, Pelchen-Matthews A (2000) Endocytosis in viral replication. Traffic 1:525–532

    CAS  PubMed  Google Scholar 

  • McArthur JC, Steiner J, Sacktor N, Nath A (2010) Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol 67:699–714

    CAS  PubMed  Google Scholar 

  • McCarthy GF, Leblond CP (1988) Radioautographic evidence for slow astrocyte turnover and modest oligodendrocyte production in the corpus callosum of adult mice infused with 3H-thymidine. J Comp Neurol 271:589–603

    CAS  PubMed  Google Scholar 

  • McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ (2003) Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300:1295–1297

    CAS  PubMed  Google Scholar 

  • Mellman I (1996) Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 12:575–625

    CAS  PubMed  Google Scholar 

  • Merrill JE, Benveniste EN (1996) Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 19:331–338

    CAS  PubMed  Google Scholar 

  • Messam CA, Major EO (2000) Stages of restricted HIV-1 infection in astrocyte cultures derived from human fetal brain tissue. J Neurovirol 6(1):S90–S94

    PubMed  Google Scholar 

  • Nath A, Hartloper V, Furer M, Fowke KR (1995) Infection of human fetal astrocytes with HIV-1: viral tropism and the role of cell to cell contact in viral transmission. J Neuropathol Exp Neurol 54:320–330

    CAS  PubMed  Google Scholar 

  • Navia BA, Cho ES, Petito CK, Price RW (1986) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19:525–535

    CAS  PubMed  Google Scholar 

  • Neumann M, Felber BK, Kleinschmidt A, Froese B, Erfle V, Pavlakis GN, Brack-Werner R (1995) Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function. J Virol 69:2159–2167

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nikolic DS, Lehmann M, Felts R, Garcia E, Blanchet FP, Subramaniam S, Piguet V (2011) HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation. Blood 118:4841–4852

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH, Sharer LR, McComb RD, Swindells S, Soderland C, Gendelman HE (1996) Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol 156:1284–1295

    CAS  PubMed  Google Scholar 

  • Orandle MS, MacLean AG, Sasseville VG, Alvarez X, Lackner AA (2002) Enhanced expression of proinflammatory cytokines in the central nervous system is associated with neuroinvasion by simian immunodeficiency virus and the development of encephalitis. J Virol 76:5797–5802

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park IW, He JJ (2009) HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants. J Leukoc Biol 86:1171–1178

    CAS  PubMed  Google Scholar 

  • Perno CF, Newcomb FM, Davis DA, Aquaro S, Humphrey RW, Calio R, Yarchoan R (1998) Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus. J Infect Dis 178:413–422

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Pomerantz RJ, Seshamma T, Trono D (1992) Efficient replication of human immunodeficiency virus type 1 requires a threshold level of Rev: potential implications for latency. J Virol 66:1809–1813

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R, Haapasalo H, Krohn K (1995) Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9:1001–1008

    CAS  PubMed  Google Scholar 

  • Rho MB, Wesselingh S, Glass JD, McArthur JC, Choi S, Griffin J, Tyor WR (1995) A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia. Brain Behav Immun 9:366–377

    CAS  PubMed  Google Scholar 

  • Riezman H, Woodman PG, van Meer G, Marsh M (1997) Molecular mechanisms of endocytosis. Cell 91:731–738

    CAS  PubMed  Google Scholar 

  • Roberts ES, Burudi EM, Flynn C, Madden LJ, Roinick KL, Watry DD, Zandonatti MA, Taffe MA, Fox HS (2004) Acute SIV infection of the brain leads to upregulation of IL6 and interferon-regulated genes: expression patterns throughout disease progression and impact on neuroAIDS. J Neuroimmunol 157:81–92

    CAS  PubMed  Google Scholar 

  • Rohr O, Marban C, Aunis D, Schaeffer E (2003) Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J Leukoc Biol 74:736–749

    CAS  PubMed  Google Scholar 

  • Rottman JB, Ganley KP, Williams K, Wu L, Mackay CR, Ringler DJ (1997) Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am J Pathol 151:1341–1351

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rudnicka D, Feldmann J, Porrot F, Wietgrefe S, Guadagnini S, Prevost MC, Estaquier J, Haase AT, Sol-Foulon N, Schwartz O (2009) Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses. J Virol 83:6234–6246

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sabri F, Tresoldi E, Di Stefano M, Polo S, Monaco MC, Verani A, Fiore JR, Lusso P, Major E, Chiodi F, Scarlatti G (1999) Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors. Virology 264:370–384

    CAS  PubMed  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 Neurovirol 8:136–142

    PubMed  Google Scholar 

  • Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44:474–481

    CAS  PubMed  Google Scholar 

  • Sattentau Q (2008) Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 6:815–826

    CAS  PubMed  Google Scholar 

  • Sattentau QJ (2010) Cell-to-cell spread of retroviruses. Viruses 2:1306–1321

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 84:2395–2407

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shahabuddin M, Volsky B, Kim H, Sakai K, Volsky DJ (1992) Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus. Pathobiology 60:195–205

    CAS  PubMed  Google Scholar 

  • Sherer NM, Lehmann MJ, Jimenez-Soto LF, Horensavitz C, Pypaert M, Mothes W (2007) Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nat Cell Biol 9:310–315

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, Baltimore D (2011) Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature 477:95–98

    CAS  PubMed  Google Scholar 

  • Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9:727–728

    CAS  PubMed  Google Scholar 

  • Sourisseau M, Sol-Foulon N, Porrot F, Blanchet F, Schwartz O (2007) Inefficient human immunodeficiency virus replication in mobile lymphocytes. J Virol 81:1000–1012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau Q, Davis DM (2008) Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol 10:211–219

    CAS  PubMed  Google Scholar 

  • Stanley LC, Mrak RE, Woody RC, Perrot LJ, Zhang S, Marshak DR, Nelson SJ, Griffin WS (1994) Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J Neuropathol Exp Neurol 53:231–238

    CAS  PubMed  Google Scholar 

  • Tanabe S, Heesen M, Berman MA, Fischer MB, Yoshizawa I, Luo Y, Dorf ME (1997) Murine astrocytes express a functional chemokine receptor. J Neurosci 17:6522–6528

    CAS  PubMed  Google Scholar 

  • Tornatore C, Nath A, Amemiya K, Major EO (1991) Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. J Virol 65:6094–6100

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Wahl SM, Allen JB, McCartney-Francis N, Morganti-Kossmann MC, Kossmann T, Ellingsworth L, Mai UE, Mergenhagen SE, Orenstein JM (1991) Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med 173:981–991

    CAS  PubMed  Google Scholar 

  • Waki K, Freed EO (2010) Macrophages and cell–cell spread of HIV-1. Viruses 2:1603–1620

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weihe E, Nohr D, Sharer L, Murray E, Rausch D, Eiden L (1993) Cortical astrocytosis in juvenile rhesus monkeys infected with simian immunodeficiency virus. Neuroreport 4:263–266

    CAS  PubMed  Google Scholar 

  • Williams KC, Hickey WF (1996) Traffic of lymphocytes into the CNS during inflammation and HIV infection. J Neuro AIDS 1:31–55

    CAS  Google Scholar 

  • Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, Adams RJ, Bartizal C, Varrone J, Rabi SA, Graham DR, Tarwater PM, Mankowski JL, Clements JE (2010) Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA. J Infect Dis 202:161–170

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Dr. Benjamin Chen of Mount Sinai School of Medicine for gagi and NLGi plasmids and Dr. I. Sadowski and Dr. S. Viviana of University of British Columbia, Canada, for RGH plasmid. We would also like to thank Drs. Anuja Ghorpade, Robert Wordinger and Porunelloor Mathew for their advices and inputs throughout the study. This work was supported in part by the grants NIH/NINDS R01NS065785 and NIH/NIMH R01MH092673 (to JJH) from National Institutes of Health.

Conflict of interest

The authors declare no conflict of interest.

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  1. Department of Cell Biology and Immunology, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA

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  2. Johnny J. He
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Luo, X., He, J.J. Cell–cell contact viral transfer contributes to HIV infection and persistence in astrocytes. J. Neurovirol. 21, 66–80 (2015). https://doi.org/10.1007/s13365-014-0304-0

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  • DOI: https://doi.org/10.1007/s13365-014-0304-0

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