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The Journal of Immunology, 1999, 162: 6263-6267.
Copyright © 1999 by The American Association of Immunologists

T Cell-Tropic HIV gp120 Mediates CD4 and CD8 Cell Chemotaxis through CXCR4 Independent of CD4: Implications for HIV Pathogenesis1

Sujatha Iyengar*,{dagger}, David H. Schwartz* and James E. K. Hildreth2,{dagger}

* Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, and {dagger} Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205

HIV entry is determined by one or more chemokine receptors. T cell-tropic viruses bind CXCR4, whereas macrophage-tropic viruses use CCR5 and other CCRs. Infection with CXCR4 and CCR5-tropic HIV requires initial binding to CD4, and chemotaxis induced by the CCR5-tropic envelope has been reported to be strictly dependent on CD4 binding. We demonstrate that, in contrast to CD4-dependent gp120 signaling via CCR5, envelope signaling through CXCR4 is CD4 independent, inducing chemotaxis of both CD4 and CD8 T cells. Signaling by virus or soluble envelope through CXCR4 may affect pathogenesis by attracting and activating target and effector cells.




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