The proline-rich region of HIV-1 Nef affects CXCR4-mediated chemotaxis in Jurkat T cells |
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Authors: | Lee Carol Man Yuk Gala Salvador Stewart Graeme John Williamson Peter |
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Institution: | The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Sydney, New South Wales, Australia. ca.lee@garvan.org.au |
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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. |
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