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

Publication ,  Journal Article
Masci, AM; Galgani, M; Cassano, S; De Simone, S; Gallo, A; De Rosa, V; Zappacosta, S; Racioppi, L
Published in: J Leukoc Biol
December 2003

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-1alpha 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.

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Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

December 2003

Volume

74

Issue

6

Start / End Page

1117 / 1124

Location

England

Related Subject Headings

  • Sulfonamides
  • Monocytes
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Isoquinolines
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • Enzyme Inhibitors
  • Dendritic Cells
 

Citation

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Masci, A. M., Galgani, M., Cassano, S., De Simone, S., Gallo, A., De Rosa, V., … Racioppi, L. (2003). HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling. J Leukoc Biol, 74(6), 1117–1124. https://doi.org/10.1189/jlb.0503239
Masci, Anna Maria, Mario Galgani, Silvana Cassano, Salvatore De Simone, Adriana Gallo, Veronica De Rosa, Serafino Zappacosta, and Luigi Racioppi. “HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling.J Leukoc Biol 74, no. 6 (December 2003): 1117–24. https://doi.org/10.1189/jlb.0503239.
Masci AM, Galgani M, Cassano S, De Simone S, Gallo A, De Rosa V, et al. HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling. J Leukoc Biol. 2003 Dec;74(6):1117–24.
Masci, Anna Maria, et al. “HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling.J Leukoc Biol, vol. 74, no. 6, Dec. 2003, pp. 1117–24. Pubmed, doi:10.1189/jlb.0503239.
Masci AM, Galgani M, Cassano S, De Simone S, Gallo A, De Rosa V, Zappacosta S, Racioppi L. HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling. J Leukoc Biol. 2003 Dec;74(6):1117–1124.

Published In

J Leukoc Biol

DOI

ISSN

0741-5400

Publication Date

December 2003

Volume

74

Issue

6

Start / End Page

1117 / 1124

Location

England

Related Subject Headings

  • Sulfonamides
  • Monocytes
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Isoquinolines
  • Immunology
  • Humans
  • HIV-1
  • HIV Envelope Protein gp120
  • Enzyme Inhibitors
  • Dendritic Cells