The proline-rich region of HIV-1 Nef affects CXCR4-mediated chemotaxis in Jurkat T cells

Viral Immunol. 2008 Sep;21(3):347-54. doi: 10.1089/vim.2007.0093.

Abstract

T-cell chemotaxis constitutes an essential function of the immune response, since active secretion of chemokines controls homing and recruitment of leukocytes into tissues. Modification of chemotactic responses by HIV-1 may provide a mechanism to increase viral spread, and may be an important factor in HIV-1 disease progression and pathogenesis. One potent T-cell chemoattractant is SDF-1 alpha, the natural ligand for the HIV-1 co-receptor CXCR4. In addition, the HIV-1 gp120 molecule shares the chemotactic properties of several chemokines, including SDF-1 alpha. HIV-1 Nef is a pathogenic determinant and a virulence factor that has pleiotropic effects on immune cell processes and receptor signaling. In this study, the effects of Nef on T-cell migration to SDF-1 alpha, and on CXCR4 receptor signaling were examined. We report that disruption of the proline-rich region of Nef inhibits T-cell migration to SDF-1 alpha. This dominant negative effect indicates that Nef occupies a position in the CXCR4-mediated signaling pathway that is upstream of an SH3-dependent pathway. The results suggest that Nef may play an important role in homing of T cells during viral invasion in HIV-1 disease.

MeSH terms

  • Amino Acid Motifs
  • Cell Movement
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / immunology
  • Chemotaxis, Leukocyte*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Jurkat Cells
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology*
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • nef Gene Products, Human Immunodeficiency Virus / chemistry*
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Chemokine CXCL12
  • Receptors, CXCR4
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1