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Science 11 July 1986:
Vol. 233. no. 4760, pp. 215 - 219
DOI: 10.1126/science.3014648
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Articles

Science, Vol 233, Issue 4760, 215-219
Copyright © 1986 by American Association for the Advancement of Science

articles

The role of mononuclear phagocytes in HTLV-III/LAV infection

S Gartner, P Markovits, DM Markovitz, MH Kaplan, RC Gallo, and M Popovic

Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.


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Viral and host cofactors facilitate HIV-1 replication in macrophages.
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B. Dey, C. S. Del Castillo, and E. A. Berger (2003)
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S. Sonza, H. P. Mutimer, K. O'Brien, P. Ellery, J. L. Howard, J. H. Axelrod, N. J. Deacon, S. M. Crowe, and D. F. J. Purcell (2002)
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Impaired Regulation of HLA-DR Expression in Human Immunodeficiency Virus-Infected Monocytes.
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T. Miyakawa, K. Obaru, K. Maeda, S. Harada, and H. Mitsuya (2002)
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D. A. Davis, E. Read-Connole, K. Pearson, H. M. Fales, F. M. Newcomb, J. Moskovitz, and R. Yarchoan (2002)
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S. Asin, G. D. Bren, E. M. Carmona, N. J. Solan, and C. V. Paya (2001)
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J. Virol. 75, 5812-5822
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Induction of Neutralizing Antibodies and Gag-Specific Cellular Immune Responses to an R5 Primary Isolate of Human Immunodeficiency Virus Type 1 in Rhesus Macaques.
D. C. Montefiori, J. T. Safrit, S. L. Lydy, A. P. Barry, M. Bilska, H. T. T. Vo, M. Klein, J. Tartaglia, H. L. Robinson, and B. Rovinski (2001)
J. Virol. 75, 5879-5890
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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)
J. Antimicrob. Chemother. 47, 819-827
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Construction and Analysis of an Infectious Human Immunodeficiency Virus Type 1 Subtype C Molecular Clone.
T. Ndung'u, B. Renjifo, and M. Essex (2001)
J. Virol. 75, 4964-4972
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The Maturation of Dendritic Cells Results in Postintegration Inhibition of HIV-1 Replication.
Y. Bakri, C. Schiffer, V. Zennou, P. Charneau, E. Kahn, A. Benjouad, J. C. Gluckman, and B. Canque (2001)
J. Immunol. 166, 3780-3788
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Simian Immunodeficiency Virus Replicates to High Levels in Naturally Infected African Green Monkeys without Inducing Immunologic or Neurologic Disease.
S. R. Broussard, S. I. Staprans, R. White, E. M. Whitehead, M. B. Feinberg, and J. S. Allan (2001)
J. Virol. 75, 2262-2275
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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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PMS-601, a New Platelet-Activating Factor Receptor Antagonist That Inhibits Human Immunodeficiency Virus Replication and Potentiates Zidovudine Activity in Macrophages.
M. Martin, N. Serradji, N. Dereuddre-Bosquet, G. Le Pavec, G. Fichet, A. Lamouri, F. Heymans, J. J. Godfroid, P. Clayette, and D. Dormont (2000)
Antimicrob. Agents Chemother. 44, 3150-3154
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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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Combination of CCR5 and CXCR4 Inhibitors in Therapy of Human Immunodeficiency Virus Type 1 Infection: In Vitro Studies of Mixed Virus Infections.
S. Rusconi, S. La Seta Catamancio, P. Citterio, E. Bulgheroni, F. Croce, S. H. Herrmann, R. E. Offord, M. Galli, and M. S. Hirsch (2000)
J. Virol. 74, 9328-9332
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HIV-1 genotypes in peripheral blood monocytes.
T. Zhu (2000)
J. Leukoc. Biol. 68, 338-344
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Linkage of the CCR5{Delta}32 Mutation with a Functional Polymorphism of CD45RA.
H.-X. Liao, D. C. Montefiori, D. D. Patel, D. M. Lee, W. K. Scott, M. Pericak-Vance, and B. F. Haynes (2000)
J. Immunol. 165, 148-157
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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. Rubsamen-Waigmann, and U. Dietrich (2000)
J. Virol. 74, 5403-5411
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Identification of Critical Amino Acid Residues in Human Immunodeficiency Virus Type 1 IN Required for Efficient Proviral DNA Formation at Steps prior to Integration in Dividing and Nondividing Cells.
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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Induction of Indolamine 2,3-Dioxygenase in Primary Human Macrophages by Human Immunodeficiency Virus Type 1 Is Strain Dependent.
R. S. Grant, H. Naif, S. J. Thuruthyil, N. Nasr, T. Littlejohn, O. Takikawa, and V. Kapoor (2000)
J. Virol. 74, 4110-4115
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Down Regulation of CD4 Expression following Isolation and Culture of Human Monocytes.
G. M. Graziani-Bowering and L. G. Filion (2000)
Clin. Vaccine Immunol. 7, 182-191
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Diminished Human Immunodeficiency Virus Type 1 Reverse Transcription and Nuclear Transport in Primary Macrophages Arrested in Early G1 Phase of the Cell Cycle.
N. A. Kootstra, B. M. Zwart, and H. Schuitemaker (2000)
J. Virol. 74, 1712-1717
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Evidence that immunoglobulin specificities of AIDS-related lymphoma are not directed to HIV-related antigens.
G. Cunto-Amesty, G. Przybylski, M. Honczarenko, J. G. Monroe, and L. E. Silberstein (2000)
Blood 95, 1393-1399
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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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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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Granulocyte-Macrophage Colony-Stimulating Factor Upregulates Reduced 5-Lipoxygenase Metabolism in Peripheral Blood Monocytes and Neutrophils in Acquired Immunodeficiency Syndrome.
M. J. Coffey, S. M. Phare, S. Cinti, M. Peters-Golden, and P. H. Kazanjian (1999)
Blood 94, 3897-3905
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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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Analysis of the Critical Domain in the V3 Loop of Human Immunodeficiency Virus Type 1 gp120 Involved in CCR5 Utilization.
C.-S. Hung, N. Vander Heyden, and L. Ratner (1999)
J. Virol. 73, 8216-8226
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TNF-{alpha} Inhibits HIV-1 Replication in Peripheral Blood Monocytes and Alveolar Macrophages by Inducing the Production of RANTES and Decreasing C-C Chemokine Receptor 5 (CCR5) Expression.
B. R. Lane, D. M. Markovitz, N. L. Woodford, R. Rochford, R. M. Strieter, and M. J. Coffey (1999)
J. Immunol. 163, 3653-3661
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