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Science 12 November 1993:
Vol. 262. no. 5136, pp. 1011 - 1018
DOI: 10.1126/science.8235617

Articles

Science, Vol 262, Issue 5136, 1011-1018
Copyright © 1993 by American Association for the Advancement of Science


articles

Multifactorial nature of human immunodeficiency virus disease: implications for therapy

AS Fauci

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

The immunopathogenic mechanisms underlying human immunodeficiency virus (HIV) disease are extremely complex; the disease process is multifactorial with multiple overlapping phases. Viral burden is substantial and viral replication occurs throughout the entire course of HIV infection. Inappropriate immune activation and elevated secretion of certain cytokines compound the pathogenic process. Profound immunosuppression ultimately occurs together with a disruption of the microenvironment of the immune system, which is probably unable to regenerate spontaneously. Thus, therapeutic strategies in HIV disease must not be unidimensional, but rather must be linked to the complex pathogenic components of the disease and must address where feasible each of the recognized pathogenic processes for the possibility of therapeutic intervention.


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M. Baba, M. Okamoto, M. Kawamura, M. Makino, T. Higashida, T. Takashi, Y. Kimura, T. Ikeuchi, T. Tetsuka, and T. Okamoto (1998)
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A Lymph Node-Derived Cytopathic Simian Immunodeficiency Virus Mne Variant Replicates in Nonstimulated Peripheral Blood Mononuclear Cells.
J. T. Kimata, A. Mozaffarian, and J. Overbaugh (1998)
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Distinct Mechanisms Trigger Apoptosis in Human Immunodeficiency Virus Type 1-Infected and in Uninfected Bystander T Lymphocytes.
G. Herbein, C. Van Lint, J. L. Lovett, and E. Verdin (1998)
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J. Exp. Med. 186, 1365-1372
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CD4 Cross-Linking (CD4XL) Induces RAS Activation and Tumor Necrosis Factor-alpha Secretion in CD4+ T Cells.
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Tat protein induces self-perpetuating permissivity for productive HIV-1 infection.
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R. Forster, G. Schweigard, S. Johann, T. Emrich, E. Kremmer, C. Nerl, and M. Lipp (1997)
Blood 90, 520-525
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Differential Effects of Interleukin-13 on Cytomegalovirus and Human Immunodeficiency Virus Infection in Human Alveolar Macrophages.
W. C. Hatch, A. R. Freedman, D. M. Boldt-Houle, J. E. Groopman, and E. F. Terwilliger (1997)
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L. Su, R. Lee, M. Bonyhadi, H. Matsuzaki, S. Forestell, S. Escaich, E. Bohnlein, and H. Kaneshima (1997)
Blood 89, 2283-2290
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Severe Stress, Depressive Symptoms, and Changes in Lymphocyte Subsets in Human Immunodeficiency Virus--Infected Men: A 2-Year Follow-up Study.
J. Leserman, J. M. Petitto, D. O. Perkins, J. D. Folds, R. N. Golden, and D. L. Evans (1997)
Arch Gen Psychiatry 54, 279-285
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Upregulation of c-Fos in Activated T Lymphoid and Monocytic Cells by Human Immunodeficiency Virus-1 Tat Protein.
D. Gibellini, A. Caputo, S. Capitani, M. La Placa, and G. Zauli (1997)
Blood 89, 1654-1664
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A Cysteine Protease Inhibitor Prevents Activation-Induced T-Cell Apoptosis and Death of Peripheral Blood Cells From Human Immunodeficiency Virus-Infected Individuals by Inhibiting Upregulation of Fas Ligand.
Y. Yang, Z.-H. Liu, C. F. Ware, and J. D. Ashwell (1997)
Blood 89, 550-557
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Differential Susceptibility to HIV-GP120-Sensitized Apoptosis in CD4+ T-Cell Clones With Different T-Helper Phenotypes: Role of CD95/CD95L Interactions.
P. Accornero, M. Radrizzani, D. Delia, F. Gerosa, R. Kurrle, and M. P. Colombo (1997)
Blood 89, 558-569
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Interleukin (IL) 1beta , IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: Pathophysiological implications.
M.-L. Wong, P. B. Bongiorno, V. Rettori, S. M. McCann, and J. Licinio (1997)
PNAS 94, 227-232
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Macrophage-dependent Apoptosis of CD4+ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor.
A. D. Badley, D. Dockrell, M. Simpson, R. Schut, D. H. Lynch, P. Leibson, and C. V. Paya (1997)
J. Exp. Med. 185, 55-64
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Membrane Tumor Necrosis Factor (TNF) Induced Cooperative Signaling of TNFR60 and TNFR80 Favors Induction of Cell Death Rather Than Virus Production in HIV-infected T Cells.
J. K. Lazdins, M. Grell, M. R. Walker, K. Woods-Cook, P. Scheurich, and K. Pfizenmaier (1997)
J. Exp. Med. 185, 81-90
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Hemophilia and Nonprogressing Human Immunodeficiency Virus Type 1 Infection.
E. Vicenzi, P. Bagnarelli, E. Santagostino, S. Ghezzi, M. Alfano, M. S. Sinnone, G. Fabio, L. Turchetto, G. Moretti, A. Lazzarin, et al. (1997)
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AIDS in 1996 Much Accomplished, Much to Do.
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S. Jolles, S. K. De Loes, M. A Johnson, and G. Janossy (1996)
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J. Biol. Chem. 270, 10278-10283
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