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Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor

Abstract

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) enter target cells by forming a complex between the viral envelope protein and two cell-surface membrane receptors: CD4 and a 7-span transmembrane chemokine receptor (reviewed in refs 1,2,3). Isolates of HIV that differ in cellular tropism use different subsets of chemokine receptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas T-cell-tropic and dual-tropic isolates use CXCR4 (refs 1,2,3) receptors. HIV-mediated signal transduction through CCR5 is not required for efficient fusion and entry of HIV in vitro4,5. Here we show that recombinant envelope proteins from macrophage-tropic HIV and SIV induce a signal through CCR5 on CD4+ T cells and that envelope-mediated signal transduction through CCR5 induces chemotaxis of T cells. This chemotactic response may contribute to the pathogenesis of HIV in vivo by chemo-attracting activated CD4+ cells to sites of viral replication1,2. HIV-mediated signalling through CCR5 may also enhance viral replication invivo by increasing the activation state of target cells. Alternatively, envelope-mediated CCR5 signal transduction may influence viral-associated cytopathicity or apoptosis.

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Figure 1: M-tropic gp160 induces CCR5-mediated calcium signalling in B10 cells.
Figure 2: M-tropic HIV and SIV gp160 induce CCR5-mediated calcium signalling in anti-CD3 mAb plus IL-2-stimulated CD4+ T cells.
Figure 3: HIV and SIV M-tropic but not T-tropic envelopes are chemotactic for activated CD4+ T cells.

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Correspondence to Drew Weissman.

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Weissman, D., Rabin, R., Arthos, J. et al. Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor. Nature 389, 981–985 (1997). https://doi.org/10.1038/40173

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