science pharmaceutical expo biotech jobs
Originally published online as doi:10.1189/jlb.0503239 on September 12, 2003

Published online before print September 12, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0503239v1
74/6/1117    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Masci, A. M.
Right arrow Articles by Racioppi, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Masci, A. M.
Right arrow Articles by Racioppi, L.
(Journal of Leukocyte Biology. 2003;74:1117-1124.)
© 2003 by Society for Leukocyte Biology

HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling

Anna Maria Masci*, Mario Galgani*, Silvana Cassano{dagger}, Salvatore De Simone{dagger}, Adriana Gallo{dagger}, Veronica De Rosa*, Serafino Zappacosta* and Luigi Racioppi*,1

* Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Naples, Italy; and
{dagger} Istituto di Endocrinologia ed Oncologia Sperimentale, Napoli, Italy

1 Correspondence: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, 5 via S. Pansini, I-80131 Napoli, Italy. E-mail: racioppi{at}unina.it

The ability of the envelope glycoprotein gp120 [human immunodeficiency virus (HIV) env] to induce intracellular signals is thought to contribute to HIV-1 pathogenesis. In the present study, we found that the exposure of CD4+ CD45RA+ naive T cells to HIVenv results in a long-lasting hyporesponsiveness to antigen stimulation. This phenomenon is not dependent on CD4-mediated signals and also can be generated by the exposure of naive T cell to soluble CD4-HIVenv complexes. The analysis of the proximal signaling reveals that HIVenv does not activate Lck as well as the mitogen-activated protein kinase intermediate cascade. Conversely, the envelope glycoprotein stimulates the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activity and induces the progressive accumulation of the phosphorylated form of the cAMP-responsive element binding. Of note, the ligation of CXCR4 by stromal cell-derived factor-1{alpha} but not the engagement of CD4 by monoclonal antibody stimulates the PKA activity and induces a long-lasting hyporesponsivity state in naive CD4+ lymphocytes. The pretreatment of lymphocytes with H89, a cell-permeable PKA inhibitor, prevents the induction of anergy. These findings reveal a novel mechanism by which HIVenv may modulate the processes of clonal expansion, homeostatic proliferation, and terminal differentiation of the naive T lymphocyte subset.

Key Words: CXCR4 • HIVenv • cAMP • CREB




This article has been cited by other articles:


Home page
 J. Virol.Home page
B. Harmon and L. Ratner
Induction of the G{alpha}q Signaling Cascade by the Human Immunodeficiency Virus Envelope Is Required for Virus Entry
J. Virol., September 15, 2008; 82(18): 9191 - 9205.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Hajishengallis, M. Wang, S. Liang, M. Triantafilou, and K. Triantafilou
Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function
PNAS, September 9, 2008; 105(36): 13532 - 13537.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Bostik, E. S. Noble, S. T. Stephenson, F. Villinger, and A. A. Ansari
CD4+ T Cells from Simian Immunodeficiency Virus Disease-Resistant Sooty Mangabeys Produce More IL-2 Than Cells from Disease-Susceptible Species: Involvement of p300 and CREB at the Proximal IL-2 Promoter in IL-2 Up-Regulation
J. Immunol., June 15, 2007; 178(12): 7720 - 7729.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Liang, M. Wang, K. Triantafilou, M. Triantafilou, H. F. Nawar, M. W. Russell, T. D. Connell, and G. Hajishengallis
The A Subunit of Type IIb Enterotoxin (LT-IIb) Suppresses the Proinflammatory Potential of the B Subunit and Its Ability to Recruit and Interact with TLR2
J. Immunol., April 15, 2007; 178(8): 4811 - 4819.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
K. Fernando, H. Hu, H. Ni, J. A. Hoxie, and D. Weissman
Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses
Blood, March 15, 2007; 109(6): 2538 - 2544.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Martinelli, C. Cicala, D. Van Ryk, D. J. Goode, K. Macleod, J. Arthos, and A. S. Fauci
HIV-1 gp120 inhibits TLR9-mediated activation and IFN-{alpha} secretion in plasmacytoid dendritic cells
PNAS, February 27, 2007; 104(9): 3396 - 3401.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Giordano, D. M. Magaletti, and E. A. Clark
Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19
Blood, February 15, 2006; 107(4): 1537 - 1545.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C.-A. Amella, B. Sherry, D. H. Shepp, and H. Schmidtmayerova
Macrophage Inflammatory Protein 1{alpha} Inhibits Postentry Steps of Human Immunodeficiency Virus Type 1 Infection via Suppression of Intracellular Cyclic AMP
J. Virol., May 1, 2005; 79(9): 5625 - 5631.
[Abstract] [Full Text] [PDF]