Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 22 December 1989:
Vol. 246. no. 4937, pp. 1606 - 1608
DOI: 10.1126/science.2556795
Prev | Table of Contents | Next

Articles

Science, Vol 246, Issue 4937, 1606-1608
Copyright © 1989 by American Association for the Advancement of Science

articles

Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1

RP Viscidi, K Mayur, HM Lederman, and AD Frankel

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

The purified human immunodeficiency virus type-l (HIV-l) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ubiquitin-Independent Degradation of Hepatitis C Virus F Protein.
K. Yuksek, W.-l. Chen, D. Chien, and J.-h. J. Ou (2009)
J. Virol. 83, 612-621
   Abstract »    Full Text »    PDF »
Tat-Induced FOXO3a Is a Key Mediator of Apoptosis in HIV-1-Infected Human CD4+ T Lymphocytes.
A. Dabrowska, N. Kim, and A. Aldovini (2008)
J. Immunol. 181, 8460-8477
   Abstract »    Full Text »    PDF »
HIV-1 Tat Mediates Degradation of RON Receptor Tyrosine Kinase, a Regulator of Inflammation.
P. Kalantari, O. F. Harandi, P. A. Hankey, and A. J. Henderson (2008)
J. Immunol. 181, 1548-1555
   Abstract »    Full Text »    PDF »
HIV-1 Tat Suppresses gp120-Specific T Cell Response in IL-10-Dependent Manner.
S. Gupta, R. Boppana, G. C. Mishra, B. Saha, and D. Mitra (2008)
J. Immunol. 180, 79-88
   Abstract »    Full Text »    PDF »
Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha.
B. Majumder, N. J. Venkatachari, E. A. Schafer, M. L. Janket, and V. Ayyavoo (2007)
J. Virol. 81, 7388-7399
   Abstract »    Full Text »    PDF »
HIV-1 Tat Raises an Adjuvant-free Humoral Immune Response Controlled by Its Core Region and Its Ability to Form Cysteine-mediated Oligomers.
J. Kittiworakarn, A. Lecoq, G. Moine, R. Thai, E. Lajeunesse, P. Drevet, C. Vidaud, A. Menez, and M. Leonetti (2006)
J. Biol. Chem. 281, 3105-3115
   Abstract »    Full Text »    PDF »
Improved Vaccine Protection from Simian AIDS by the Addition of Nonstructural Simian Immunodeficiency Virus Genes.
Z. Hel, W.-P. Tsai, E. Tryniszewska, J. Nacsa, P. D. Markham, M. G. Lewis, G. N. Pavlakis, B. K. Felber, J. Tartaglia, and G. Franchini (2006)
J. Immunol. 176, 85-96
   Abstract »    Full Text »    PDF »
Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8+ T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase of Bordetella pertussis.
L. Mascarell, C. Fayolle, C. Bauche, D. Ladant, and C. Leclerc (2005)
J. Virol. 79, 9872-9884
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 1 Vpr Impairs Dendritic Cell Maturation and T-Cell Activation: Implications for Viral Immune Escape.
B. Majumder, M. L. Janket, E. A. Schafer, K. Schaubert, X.-L. Huang, J. Kan-Mitchell, C. R. Rinaldo Jr., and V. Ayyavoo (2005)
J. Virol. 79, 7990-8003
   Abstract »    Full Text »    PDF »
Sequence Variation within the Dominant Amino Terminus Epitope Affects Antibody Binding and Neutralization of Human Immunodeficiency Virus Type 1 Tat Protein.
T. J. Ruckwardt, I. Tikhonov, S. Berg, G. S. Hatfield, A. Chandra, P. Chandra, B. Gilliam, R. R. Redfield, R. C. Gallo, and C. D. Pauza (2004)
J. Virol. 78, 13190-13196
   Abstract »    Full Text »    PDF »
The Glutamine-rich Region of the HIV-1 Tat Protein Is Involved in T-cell Apoptosis.
G. R. Campbell, E. Pasquier, J. Watkins, V. Bourgarel-Rey, V. Peyrot, D. Esquieu, P. Barbier, J. de Mareuil, D. Braguer, P. Kaleebu, et al. (2004)
J. Biol. Chem. 279, 48197-48204
   Abstract »    Full Text »    PDF »
Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides.
E. Moreau, G. Belliard, C. D. Partidos, F. Pradezinsky, H. Le Buanec, S. Muller, and C. Desgranges (2004)
J. Gen. Virol. 85, 2893-2901
   Abstract »    Full Text »    PDF »
Codon Optimization of the Tat Antigen of Human Immunodeficiency Virus Type 1 Generates Strong Immune Responses in Mice following Genetic Immunization.
L. Ramakrishna, K. K. Anand, K. M. Mohankumar, and U. Ranga (2004)
J. Virol. 78, 9174-9189
   Abstract »    Full Text »    PDF »
Noninfectious X4 but Not R5 Human Immunodeficiency Virus Type 1 Virions Inhibit Humoral Immune Responses in Human Lymphoid Tissue Ex Vivo.
W. Fitzgerald, A. W. Sylwester, J.-C. Grivel, J. D. Lifson, and L. B. Margolis (2004)
J. Virol. 78, 7061-7068
   Abstract »    Full Text »    PDF »
Generation and Characterization of Neutralizing Human Monoclonal Antibodies against Human Immunodeficiency Virus Type 1 Tat Antigen.
E. Moreau, J. Hoebeke, D. Zagury, S. Muller, and C. Desgranges (2004)
J. Virol. 78, 3792-3796
   Abstract »    Full Text »    PDF »
Measurements of HIV Viral Loads From Different Levels of the Respiratory Tract.
K. L. Wood, P. Chaiyarit, R. B. Day, Y. Wang, C. T. Schnizlein-Bick, R. L. Gregory, and H. L. Twigg III (2003)
Chest 124, 536-542
   Abstract »    Full Text »    PDF »
Tat-Neutralizing Antibodies in Vaccinated Macaques.
I. Tikhonov, T. J. Ruckwardt, G. S. Hatfield, and C. D. Pauza (2003)
J. Virol. 77, 3157-3166
   Abstract »    Full Text »    PDF »
Tat HIV-1 Primary and Tertiary Structures Critical to Immune Response Against Non-homologous Variants.
S. Opi, J.-M. Peloponese Jr., D. Esquieu, G. Campbell, J. de Mareuil, A. Walburger, M. Solomiac, C. Gregoire, E. Bouveret, D. L. Yirrell, et al. (2002)
J. Biol. Chem. 277, 35915-35919
   Abstract »    Full Text »    PDF »
A Tat subunit vaccine confers protective immunity against the immune-modulating activity of the human immunodeficiency virus type-1 Tat protein in mice.
S. M. Agwale, M. T. Shata, M. S. Reitz Jr., V. S. Kalyanaraman, R. C. Gallo, M. Popovic, and D. M. Hone (2002)
PNAS 99, 10037-10041
   Abstract »    Full Text »    PDF »
Tat Acetyl-acceptor Lysines Are Important for Human Immunodeficiency Virus Type-1 Replication.
V. Bres, R. Kiernan, S. Emiliani, and M. Benkirane (2002)
J. Biol. Chem. 277, 22215-22221
   Abstract »    Full Text »    PDF »
Angiogenic Effects of Extracellular Human Immunodeficiency Virus Type 1 Tat Protein and Its Role in the Pathogenesis of AIDS-Associated Kaposi's Sarcoma.
G. Barillari and B. Ensoli (2002)
Clin. Microbiol. Rev. 15, 310-326
   Abstract »    Full Text »    PDF »
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction.
M. H. Glickman and A. Ciechanover (2002)
Physiol Rev 82, 373-428
   Abstract »    Full Text »    PDF »
Outcome of Simian-Human Immunodeficiency Virus Strain 89.6p Challenge following Vaccination of Rhesus Macaques with Human Immunodeficiency Virus Tat Protein.
P. Silvera, M. W. Richardson, J. Greenhouse, J. Yalley-Ogunro, N. Shaw, J. Mirchandani, K. Khalili, J.-F. Zagury, M. G. Lewis, and J. Rappaport (2002)
J. Virol. 76, 3800-3809
   Abstract »    Full Text »    PDF »
Native HIV-1 Tat Protein Targets Monocyte-Derived Dendritic Cells and Enhances Their Maturation, Function, and Antigen-Specific T Cell Responses.
E. Fanales-Belasio, S. Moretti, F. Nappi, G. Barillari, F. Micheletti, A. Cafaro, and B. Ensoli (2002)
J. Immunol. 168, 197-206
   Abstract »    Full Text »    PDF »
Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway.
A. Badou, Y. Bennasser, M. Moreau, C. Leclerc, M. Benkirane, and E. Bahraoui (2000)
J. Virol. 74, 10551-10562
   Abstract »    Full Text »
The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-kappa B Consensus Sites.
S. P. Lim and A. Garzino-Demo (2000)
J. Virol. 74, 1632-1640
   Abstract »    Full Text »
Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge.
S. S. Cohen, C. Li, L. Ding, Y. Cao, A. B. Pardee, E. M. Shevach, and D. I. Cohen (1999)
PNAS 96, 10842-10847
   Abstract »    Full Text »    PDF »
Tat as one key to HIV-induced immune pathogenesis and Pat toxoid as an important component of a vaccine.
R. C. Gallo (1999)
PNAS 96, 8324-8326
   Full Text »    PDF »
Human Immunodeficiency Virus Type 2 Produces a Defect in CD3-gamma Gene Transcripts Similar to That Observed for Human Immunodeficiency Virus Type 1.
I. Segura, C. Delmelle-Wibaut, M. Janssens, Y. Cleuter, A. van den Broeke, R. Kettmann, and K. E. Willard-Gallo (1999)
J. Virol. 73, 5207-5213
   Abstract »    Full Text »
Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase.
V. N. Gladyshev, T. C. Stadtman, D. L. Hatfield, and K.-T. Jeang (1999)
PNAS 96, 835-839
   Abstract »    Full Text »    PDF »
HIV-1 Tat Inhibits Human Natural Killer Cell Function by Blocking L-Type Calcium Channels.
M. R. Zocchi, A. Rubartelli, P. Morgavi, and A. Poggi (1998)
J. Immunol. 161, 2938-2943
   Abstract »    Full Text »    PDF »
The Basic Domain in HIV-1 Tat Protein as a Target for Polysulfonated Heparin-mimicking Extracellular Tat Antagonists.
M. Rusnati, G. Tulipano, C. Urbinati, E. Tanghetti, R. Giuliani, M. Giacca, M. Ciomei, A. Corallini, and M. Presta (1998)
J. Biol. Chem. 273, 16027-16037
   Abstract »    Full Text »    PDF »
Extracellular HIV-1 Tat Protein Induces the Rapid Ser133 Phosphorylation and Activation of CREB Transcription Factor in Both Jurkat Lymphoblastoid T Cells and Primary Peripheral Blood Mononuclear Cells.
D. Gibellini, A. Bassini, S. Pierpaoli, L. Bertolaso, D. Milani, S. Capitani, M. La Placa, and G. Zauli (1998)
J. Immunol. 160, 3891-3898
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Interferon alpha  and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS.
D. Zagury, A. Lachgar, V. Chams, L. S. Fall, J. Bernard, J.-F. Zagury, B. Bizzini, A. Gringeri, E. Santagostino, J. Rappaport, et al. (1998)
PNAS 95, 3851-3856
   Abstract »    Full Text »    PDF »
Involvement of Dihydropyridine-sensitive Calcium Channels in Human Dendritic Cell Function. COMPETITION BY HIV-1 TAT.
A. Poggi, A. Rubartelli, and M. R. Zocchi (1998)
J. Biol. Chem. 273, 7205-7209
   Abstract »    Full Text »    PDF »
Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis.
L. Flamand, R. W. Crowley, P. Lusso, S. Colombini-Hatch, D. M. Margolis, and R. C. Gallo (1998)
PNAS 95, 3111-3116
   Abstract »    Full Text »    PDF »
Superinduction of IL-8 in T Cells by HIV-1 Tat Protein Is Mediated Through NF-{kappa}B Factors.
M. Ott, J. L. Lovett, L. Mueller, and E. Verdin (1998)
J. Immunol. 160, 2872-2880
   Abstract »    Full Text »    PDF »
Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells.
M. X. Wu and S. F. Schlossman (1997)
PNAS 94, 13832-13837
   Abstract »    Full Text »    PDF »
The N-terminal Structure of HIV-1 Tat Is Required for Suppression of CD26-dependent T Cell Growth.
S. Wrenger, T. Hoffmann, J. Faust, C. Mrestani-Klaus, W. Brandt, K. Neubert, M. Kraft, S. Olek, R. Frank, S. Ansorge, et al. (1997)
J. Biol. Chem. 272, 30283-30288
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus-1-Tat Protein Induces the Cell Surface Expression of Endothelial Leukocyte Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Intercellular Adhesion Molecule-1 in Human Endothelial Cells.
S. Dhawan, R. K. Puri, A. Kumar, H. Duplan, J.-M. Masson, and B. B. Aggarwal (1997)
Blood 90, 1535-1544
   Abstract »    Full Text »    PDF »
HIV-1 Tat Induces the Expression of the Interleukin-6 (IL6) Gene by Binding to the IL6 Leader RNA and by Interacting with CAAT Enhancer-binding Protein beta  (NF-IL6) Transcription Factors.
C. Ambrosino, M. R. Ruocco, X. Chen, M. Mallardo, F. Baudi, S. Trematerra, I. Quinto, S. Venuta, and G. Scala (1997)
J. Biol. Chem. 272, 14883-14892
   Abstract »    Full Text »    PDF »
HIV-1 Tat Inhibits the 20S Proteasome and Its 11S Regulator-mediated Activation.
M. Seeger, K. Ferrell, R. Frank, and W. Dubiel (1997)
J. Biol. Chem. 272, 8145-8148
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Extracellular Human Immunodeficiency Virus Type-1 Tat Protein Activates Phosphatidylinositol 3-Kinase in PC12 Neuronal Cells.
D. Milani, M. Mazzoni, P. Borgatti, G. Zauli, L. Cantley, and S. Capitani (1996)
J. Biol. Chem. 271, 22961-22964
   Abstract »    Full Text »    PDF »
Physical and Functional Interaction of Nef with Lck.
Y. Collette, H. Dutartre, A. Benziane, F. Ramos-Morales, R. Benarous, M. Harris, and D. Olive (1996)
J. Biol. Chem. 271, 6333-6341
   Abstract »    Full Text »    PDF »
Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein.
C. Li, D. Friedman, C Wang, V Metelev, and A. Pardee (1995)
Science 268, 429-431
   Abstract »    PDF »
Participation of tyrosine phosphorylation in the cytopathic effect of human immunodeficiency virus-1.
D. Cohen, Y Tani, H Tian, E Boone, L. Samelson, and H. Lane (1992)
Science 256, 542-545
   Abstract »    PDF »
Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist.
M. Hsu, A. Schutt, M Holly, L. Slice, M. Sherman, D. Richman, M. Potash, and D. Volsky (1991)
Science 254, 1799-1802
   Abstract »    PDF »
Down-regulation of T Cell Activation following Inhibition of Dipeptidyl Peptidase IV/CD26 by the N-terminal Part of the Thromboxane A2 Receptor.
S. Wrenger, J. Faust, C. Mrestani-Klaus, A. Fengler, A. Stockel-Maschek, S. Lorey, T. Kahne, W. Brandt, K. Neubert, S. Ansorge, et al. (2000)
J. Biol. Chem. 275, 22180-22186
   Abstract »    Full Text »    PDF »
Internalization of HIV-1 Tat Requires Cell Surface Heparan Sulfate Proteoglycans.
M. Tyagi, M. Rusnati, M. Presta, and M. Giacca (2001)
J. Biol. Chem. 276, 3254-3261
   Abstract »    Full Text »    PDF »
Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques.
C. D. Pauza, P. Trivedi, M. Wallace, T. J. Ruckwardt, H. Le Buanec, W. Lu, B. Bizzini, A. Burny, D. Zagury, and R. C. Gallo (2000)
PNAS 97, 3515-3519
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)