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Science 5 September 1986:
Vol. 233. no. 4768, pp. 1089 - 1093
DOI: 10.1126/science.3016903
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Articles

Science, Vol 233, Issue 4768, 1089-1093
Copyright © 1986 by American Association for the Advancement of Science

articles

Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy

S Koenig, HE Gendelman, JM Orenstein, MC Dal Canto, GH Pezeshkpour, M Yungbluth, F Janotta, A Aksamit, MA Martin, and AS Fauci

One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.


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Interferon-{alpha} as an immunotherapeutic protein.
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Directed Egress of Animal Viruses Promotes Cell-to-Cell Spread.
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The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages.
V. Mollace, D. Salvemini, D. P. Riley, C. Muscoli, M. Iannone, T. Granato, L. Masuelli, A. Modesti, D. Rotiroti, R. Nistico, et al. (2002)
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NF-kappa B cis-Acting Motifs of the Human Immunodeficiency Virus (HIV) Long Terminal Repeat Regulate HIV Transcription in Human Macrophages.
S. Asin, G. D. Bren, E. M. Carmona, N. J. Solan, and C. V. Paya (2001)
J. Virol. 75, 11408-11416
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Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in Macrophages through a C/EBP-Dependent Mechanism.
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J. Virol. 75, 9703-9712
   Abstract »    Full Text »    PDF »
Syndecans Serve as Attachment Receptors for Human Immunodeficiency Virus Type 1 on Macrophages.
A. C. S. Saphire, M. D. Bobardt, Z. Zhang, G. David, and P. A. Gallay (2001)
J. Virol. 75, 9187-9200
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J. Virol. 75, 7925-7933
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Susceptibility of Rat-Derived Cells to Replication by Human Immunodeficiency Virus Type 1.
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J. Virol. 75, 8063-8073
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Erythrocyte-mediated delivery of a new homodinucleotide active against human immunodeficiency virus and herpes simplex virus.
L. Rossi, S. Serafini, L. Cappellacci, E. Balestra, G. Brandi, G. F. Schiavano, P. Franchetti, M. Grifantini, C.-F. Perno, and M. Magnani (2001)
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Regulation of Human Immunodeficiency Virus Type 1 Infection, {beta}-Chemokine Production, and CCR5 Expression in CD40L-Stimulated Macrophages: Immune Control of Viral Entry.
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J. Virol. 75, 4308-4320
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S. Aquaro, P. Menten, S. Struyf, P. Proost, J. Van Damme, E. De Clercq, and D. Schols (2001)
J. Virol. 75, 4402-4406
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Differential CD4/CCR5 Utilization, gp120 Conformation, and Neutralization Sensitivity between Envelopes from a Microglia-Adapted Human Immunodeficiency Virus Type 1 and Its Parental Isolate.
J. Martín, C. C. LaBranche, and F. González-Scarano (2001)
J. Virol. 75, 3568-3580
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Perivascular Macrophages Are the Primary Cell Type Productively Infected by Simian Immunodeficiency Virus in the Brains of Macaques: Implications for the Neuropathogenesis of AIDS.
K. C. Williams, S. Corey, S. V. Westmoreland, D. Pauley, H. Knight, C. deBakker, X. Alvarez, and A. A. Lackner (2001)
J. Exp. Med. 193, 905-916
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Investigation of the simian polyomavirus SV40 as a potential causative agent of human neurological disorders in AIDS patients.
M. TOGNON, F. MARTINI, L. IACCHERI, R. CULTRERA, and C. CONTINI (2001)
J. Med. Microbiol. 50, 165-172
   Abstract »    Full Text »    PDF »
HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes.
I.-W. Park, J.-F. Wang, and J. E. Groopman (2001)
Blood 97, 352-358
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T-tropic human immunodeficiency virus (HIV) type 1 Nef protein enters human monocyte-macrophages and induces resistance to HIV replication: a possible mechanism of HIV T-tropic emergence in AIDS.
L. Alessandrini, A. C. Santarcangelo, E. Olivetta, F. Ferrantelli, P. d’Aloja, K. Pugliese, E. Pelosi, C. Chelucci, G. Mattia, C. Peschle, et al. (2000)
J. Gen. Virol. 81, 2905-2917
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Mechanisms for Adaptation of Simian Immunodeficiency Virus to Replication in Alveolar Macrophages.
K. Mori, M. Rosenzweig, and R. C. Desrosiers (2000)
J. Virol. 74, 10852-10859
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Nitric Oxide Synthesis Enhances Human Immunodeficiency Virus Replication in Primary Human Macrophages.
D. Blond, H. Raoul, R. Le Grand, and D. Dormont (2000)
J. Virol. 74, 8904-8912
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Induction of the Chemokines Interleukin-8 and IP-10 by Human Immunodeficiency Virus Type 1 Tat in Astrocytes.
O. Kutsch, J.-W. Oh, A. Nath, and E. N. Benveniste (2000)
J. Virol. 74, 9214-9221
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Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia.
Y. Persidsky, J. Zheng, D. Miller, and H. E. Gendelman (2000)
J. Leukoc. Biol. 68, 413-422
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Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes.
S. Aquaro, S. Panti, M. C. Caroleo, E. Balestra, A. Cenci, F. Forbici, G. Ippolito, A. Mastino, R. Testi, V. Mollace, et al. (2000)
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Lentivirus Infection in the Brain Induces Matrix Metalloproteinase Expression: Role of Envelope Diversity.
J. B. Johnston, Y. Jiang, G. van Marle, M. B. Mayne, W. Ni, J. Holden, J. C. McArthur, and C. Power (2000)
J. Virol. 74, 7211-7220
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Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary CD4+ T Lymphocytes, Monocytes, and Dendritic Cells by Cytotoxic T Lymphocytes.
M. E. Severino, N. V. Sipsas, P. T. Nguyen, S. A. Kalams, B. D. Walker, R. P. Johnson, and O. O. Yang (2000)
J. Virol. 74, 6695-6699
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Human Immunodeficiency Virus (HIV)-Positive Sera Obtained Shortly after Seroconversion Neutralize Autologous HIV Type 1 Isolates on Primary Macrophages but Not on Lymphocytes.
H. Ruppach, P. Nara, I. Raudonat, Z. Elanjikal, H. Rübsamen-Waigmann, and U. Dietrich (2000)
J. Virol. 74, 5403-5411
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N. Tsurutani, M. Kubo, Y. Maeda, T. Ohashi, N. Yamamoto, M. Kannagi, and T. Masuda (2000)
J. Virol. 74, 4795-4806
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Lipopolysaccharide Inhibits HIV-1 Infection of Monocyte- Derived Macrophages Through Direct and Sustained Down-Regulation of CC Chemokine Receptor 5.
G. Franchin, G. Zybarth, W. W. Dai, L. Dubrovsky, N. Reiling, H. Schmidtmayerova, M. Bukrinsky, and B. Sherry (2000)
J. Immunol. 164, 2592-2601
   Abstract »    Full Text »    PDF »
Abundant Defective Viral Particles Budding from Microglia in the Course of Retroviral Spongiform Encephalopathy.
R. Hansen, S. Czub, E. Werder, J. Herold, G. Gosztonyi, H. Gelderblom, S. Schimmer, S. Mazgareanu, V. ter Meulen, and M. Czub (2000)
J. Virol. 74, 1775-1780
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Activities of Masked 2',3'-Dideoxynucleoside Monophosphate Derivatives against Human Immunodeficiency Virus in Resting Macrophages.
S. Aquaro, O. Wedgwood, C. Yarnold, D. Cahard, R. Pathinara, C. McGuigan, R. Calio', E. de Clercq, J. Balzarini, and C. F. Perno (2000)
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Activation of the PAK-Related Kinase by Human Immunodeficiency Virus Type 1 Nef in Primary Human Peripheral Blood Lymphocytes and Macrophages Leads to Phosphorylation of a PIX-p95 Complex.
A. Brown, X. Wang, E. Sawai, and C. Cheng-Mayer (1999)
J. Virol. 73, 9899-9907
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Blood-Brain Barrier Tight Junction Disruption in Human Immunodeficiency Virus-1 Encephalitis.
L. M. Dallasta, L. A. Pisarov, J. E. Esplen, J. V. Werley, A. V. Moses, J. A. Nelson, and C. L. Achim (1999)
Am. J. Pathol. 155, 1915-1927
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Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV.
E. Garaci, M. C. Caroleo, L. Aloe, S. Aquaro, M. Piacentini, N. Costa, A. Amendola, A. Micera, R. Calio, C.-F. Perno, et al. (1999)
PNAS 96, 14013-14018
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Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis.
Y. Persidsky, A. Ghorpade, J. Rasmussen, J. Limoges, X. J. Liu, M. Stins, M. Fiala, D. Way, K. S. Kim, M. H. Witte, et al. (1999)
Am. J. Pathol. 155, 1599-1611
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Infection of HIV-1 Transgenic Mice with Mycobacterium avium Induces the Expression of Infectious Virus Selectively from a Mac-1-Positive Host Cell Population.
T. M. Doherty, C. Chougnet, M. Schito, B. K. Patterson, C. Fox, G. M. Shearer, G. Englund, and A. Sher (1999)
J. Immunol. 163, 1506-1515
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Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment.
G. Schifitto, N. Sacktor, K. Marder, M. P. McDermott, J. C. McArthur, K. Kieburtz, S. Small, and L. G. Epstein (1999)
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F. Ensoli, V. Fiorelli, M. DeCristofaro, D. Santini Muratori, A. Novi, B. Vannelli, C. J. Thiele, G. Luzi, and F. Aiuti (1999)
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L. A. Boven, L. Gomes, C. Hery, F. Gray, J. Verhoef, P. Portegies, M. Tardieu, and H. S. L. M. Nottet (1999)
J. Immunol. 162, 4319-4327
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus-1-Infected Macrophages Induce Inducible Nitric Oxide Synthase and Nitric Oxide (NO) Production in Astrocytes: Astrocytic NO as a Possible Mediator of Neural Damage in Acquired Immunodeficiency Syndrome.
K. Hori, P. R. Burd, K. Furuke, J. Kutza, K. A. Weih, and K. A. Clouse (1999)
Blood 93, 1843-1850
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Human Immunodeficiency Virus Replication Induces Monocyte Chemotactic Protein-1 in Human Macrophages and U937 Promonocytic Cells.
M. Mengozzi, C. De Filippi, P. Transidico, P. Biswas, M. Cota, S. Ghezzi, E. Vicenzi, A. Mantovani, S. Sozzani, and G. Poli (1999)
Blood 93, 1851-1857
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V3 Recombinants Indicate a Central Role for CCR5 as a Coreceptor in Tissue Infection by Human Immunodeficiency Virus Type 1.
S. Y. Chan, R. F. Speck, C. Power, S. L. Gaffen, B. Chesebro, and M. A. Goldsmith (1999)
J. Virol. 73, 2350-2358
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Neuronal Death Induced by Brain-Derived Human Immunodeficiency Virus Type 1 Envelope Genes Differs between Demented and Nondemented AIDS Patients.
C. Power, J. C. McArthur, A. Nath, K. Wehrly, M. Mayne, J. Nishio, T. Langelier, R. T. Johnson, and B. Chesebro (1998)
J. Virol. 72, 9045-9053
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HIV-1 Tat Elongates the G1 Phase and Indirectly Promotes HIV-1 Gene Expression in Cells of Glial Origin.
M. Kundu, S. Sharma, A. De Luca, A. Giordano, J. Rappaport, K. Khalili, and S. Amini (1998)
J. Biol. Chem. 273, 8130-8136
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Human Immunodeficiency Virus Neurotropism: an Analysis of Viral Replication and Cytopathicity for Divergent Strains in Monocytes and Microglia.
A. Ghorpade, A. Nukuna, M. Che, S. Haggerty, Y. Persidsky, E. Carter, L. Carhart, L. Shafer, and H. E. Gendelman (1998)
J. Virol. 72, 3340-3350
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Differentiation of Promonocytic U937 Subclones into Macrophagelike Phenotypes Regulates a Cellular Factor(s) Which Modulates Fusion/Entry of Macrophagetropic Human Immunodeficiency Virus Type 1.
H. Moriuchi, M. Moriuchi, and A. S. Fauci (1998)
J. Virol. 72, 3394-3400
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Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.
K. Conant, A. Garzino-Demo, A. Nath, J. C. McArthur, W. Halliday, C. Power, R. C. Gallo, and E. O. Major (1998)
PNAS 95, 3117-3121
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Differential Tropism and Chemokine Receptor Expression of Human Immunodeficiency Virus Type 1 in Neonatal Monocytes, Monocyte-Derived Macrophages, and Placental Macrophages.
W. R. Fear, A. M. Kesson, H. Naif, G. W. Lynch, and A. L. Cunningham (1998)
J. Virol. 72, 1334-1344
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Use of Murine CXCR-4 as a Second Receptor by Some T-Cell-Tropic Human Immunodeficiency Viruses.
C. Parolin, A. Borsetti, H. Choe, M. Farzan, P. Kolchinsky, M. Heesen, Q. Ma, C. Gerard, G. Palu, M. E. Dorf, et al. (1998)
J. Virol. 72, 1652-1656
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Human Immunodeficiency Virus-1 env Impairs Fcgamma Receptor-Mediated Phagocytosis Via a Cyclic Adenosine Monophosphate-Dependent Mechanism.
C. A. Thomas, O. K. Weinberger, B. L. Ziegler, S. Greenberg, I. Schieren, S. C. Silverstein, and J. El Khoury (1997)
Blood 90, 3760-3765
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Two Orphan Seven-Transmembrane Segment Receptors Which Are Expressed in CD4-positive Cells Support Simian Immunodeficiency Virus Infection.
M. Farzan, H. Choe, K. Martin, L. Marcon, W. Hofmann, G. Karlsson, Y. Sun, P. Barrett, N. Marchand, N. Sullivan, et al. (1997)
J. Exp. Med. 186</