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Science 20 June 1997:
Vol. 276. no. 5320, pp. 1857 - 1861
DOI: 10.1126/science.276.5320.1857
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Reports

Macrophages as a Source of HIV During Opportunistic Infections

Jan M. Orenstein, * Cecil Fox, Sharon M. Wahl

The source of increasing viremia that characterizes the latter stages of human immunodeficiency virus (HIV) disease has remained a paradox because it occurs at a time when lymphoid tissue is quantitatively and qualitatively impaired, and the patients' CD4 T lymphocytes are steadily declining. Here, macrophages, both infected and uninfected with common opportunistic pathogens of HIV disease such as Mycobacterium avium complex and Pneumocystis carinii, were identified as highly productive sources of HIV in coinfected lymph nodes. These observations indicate that tissue macrophages are not only infected with HIV, but that common pathogens of HIV disease can dramatically increase their production of virus. Thus, prevention or successful treatment of opportunistic coinfections, or both, potentially benefits the patient twofold by limiting the pathology caused by opportunistic infection and by controlling induction of HIV replication.

J. M. Orenstein, Department of Pathology, George Washington University, Washington, DC 20037, USA.
C. Fox, Molecular Histology Inc., Gaithersburg, MD 20879, USA.
S. M. Wahl, Oral Infection and Immunity Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: jmo{at}gwis2.circ.gwu.edu

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   Abstract »    PDF »
Opposite Effects of IL-10 on the Ability of Dendritic Cells and Macrophages to Replicate Primary CXCR4-Dependent HIV-1 Strains.
P. Ancuta, Y. Bakri, N. Chomont, H. Hocini, D. Gabuzda, and N. Haeffner-Cavaillon (2001)
J. Immunol. 166, 4244-4253
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In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model.
C. Chougnet, C. Freitag, M. Schito, E. K. Thomas, A. Sher, and G. M. Shearer (2001)
J. Immunol. 166, 3210-3217
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The Binding Subunit of Pertussis Toxin Inhibits HIV Replication in Human Macrophages and Virus Expression in Chronically Infected Promonocytic U1 Cells.
M. Alfano, G. Vallanti, P. Biswas, C. Bovolenta, E. Vicenzi, B. Mantelli, T. Pushkarsky, R. Rappuoli, A. Lazzarin, M. Bukrinsky, et al. (2001)
J. Immunol. 166, 1863-1870
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Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans.
T. Igarashi, C. R. Brown, Y. Endo, A. Buckler-White, R. Plishka, N. Bischofberger, V. Hirsch, and M. A. Martin (2000)
PNAS
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Interferon gamma and interleukin 6 modulate the susceptibility of macrophages to human immunodeficiency virus type 1 infection.
M. Zaitseva, S. Lee, C. Lapham, R. Taffs, L. King, T. Romantseva, J. Manischewitz, and H. Golding (2000)
Blood 96, 3109-3117
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Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4+ T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines.
N. P. Juffermans, W. A. Paxton, P. E. P. Dekkers, A. Verbon, E. de Jonge, P. Speelman, S. J. H. van Deventer, and T. van der Poll (2000)
Blood 96, 2649-2654
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Permissive factors for HIV-1 infection of macrophages.
S. M. Wahl, T. Greenwell-Wild, H. Hale-Donze, N. Moutsopoulos, and J. M. Orenstein (2000)
J. Leukoc. Biol. 68, 303-310
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The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes.
A. L. Cunningham, S Li, J Juarez, G Lynch, M. Alali, and H. Naif (2000)
J. Leukoc. Biol. 68, 311-317
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Nonlymphoid reservoirs of HIV replication in children with chronic-progressive disease.
S. J. Brodie (2000)
J. Leukoc. Biol. 68, 351-359
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Biological parameters of HIV-1 infection in primary intestinal lymphocytes and macrophages.
P. D. Smith, G. Meng, M. T. Sellers, T. S. Rogers, and G. M. Shaw (2000)
J. Leukoc. Biol. 68, 360-365
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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)
J. Leukoc. Biol. 68, 429-435
   Abstract »    Full Text »    PDF »
The Synthetic Immunomodulator Murabutide Controls Human Immunodeficiency Virus Type 1 Replication at Multiple Levels in Macrophages and Dendritic Cells.
E. C. A. Darcissac, M.-J. Truong, J. Dewulf, Y. Mouton, A. Capron, and G. M. Bahr (2000)
J. Virol. 74, 7794-7802
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Differentiation of Monocytes to Macrophages Switches the Mycobacterium tuberculosis Effect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein {beta} Expression.
M. Weiden, N. Tanaka, Y. Qiao, B. Y. Zhao, Y. Honda, K. Nakata, A. Canova, D. E. Levy, W. N. Rom, and R. Pine (2000)
J. Immunol. 165, 2028-2039
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Tumor Necrosis Factor (TNF)-{alpha} and TNF Receptors in Viral Pathogenesis.
G. Herbein and W. A. O'brien (2000)
Experimental Biology and Medicine 223, 241-257
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Retrovirally Mediated IFN-{beta} Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression.
I. Cremer, V. Vieillard, and E. De Maeyer (2000)
J. Immunol. 164, 1582-1587
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Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo.
R. S. Veazey, I. C. Tham, K. G. Mansfield, M. DeMaria, A. E. Forand, D. E. Shvetz, L. V. Chalifoux, P. K. Sehgal, and A. A. Lackner (2000)
J. Virol. 74, 57-64
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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)
Antimicrob. Agents Chemother. 44, 173-177
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Cellular Compartments of Human Immunodeficiency Virus Type 1 Replication In Vivo: Determination by Presence of Virion-Associated Host Proteins and Impact of Opportunistic Infection.
S. D. Lawn, B. D. Roberts, G. E. Griffin, T. M. Folks, and S. T. Butera (2000)
J. Virol. 74, 139-145
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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.
S. Li, J. Juarez, M. Alali, D. Dwyer, R. Collman, A. Cunningham, and H. M. Naif (1999)
J. Virol. 73, 9741-9755
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Enhanced In Vivo Human Immunodeficiency Virus-1 Replication in the Lungs of Human Immunodeficiency Virus-Infected Persons with Pneumocystis carinii Pneumonia.
H. KOZIEL, S. KIM, C. REARDON, X. LI, R. GARLAND, P. PINKSTON, and H. KORNFELD (1999)
Am. J. Respir. Crit. Care Med. 160, 2048-2055
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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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Regulation of Bovine Leukemia Virus tax and pol mRNA Levels by Interleukin-2 and -10.
D. Pyeon and G. A. Splitter (1999)
J. Virol. 73, 8427-8434
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Antiretroviral-Drug Concentrations in Semen: Implications for Sexual Transmission of Human Immunodeficiency Virus Type 1.
A. D. M. Kashuba, J. R. Dyer, L. M. Kramer, R. H. Raasch, J. J. Eron, and M. S. Cohen (1999)
Antimicrob. Agents Chemother. 43, 1817-1826
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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
   Abstract »    Full Text »    PDF »


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