The proline-rich region of HIV-1 Nef affects CXCR4-mediated chemotaxis in Jurkat T cells.
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.
Lee
Carol Man Yuk
CM
The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Sydney, New South Wales, Australia. ca.lee@garvan.org.au
Gala
Salvador
S
Stewart
Graeme John
GJ
Williamson
Peter
P
D020816:Amino Acid Motifs; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1