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Published 20 January 2004. doi:10.1084/jem.20030648
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 2, 283-293
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HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse

Clare Jolly1, Kirk Kashefi2, Michael Hollinshead3, and Quentin J. Sattentau2

1 The Sir William Dunn School of Pathology, The University of Oxford, Oxford OX1 3RE, UK
2 The Jefferiss Trust Laboratories, The Wright-Fleming Institute, Imperial College Faculty of Medicine, London W2 1PG, UK
3 The Henry Wellcome Imaging Suite, The Wright-Fleming Institute, Imperial College Faculty of Medicine, London W2 1PG, UK

Address correspondence to Quentin J. Sattentau, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Phone: 01-86-52-75-511; Fax: 01-86-52-75-515; email: quentin.sattentau{at}pathology.ox.ac.uk

Direct cell–cell transfer is an efficient mechanism of viral dissemination within an infected host, and human immunodeficiency virus 1 (HIV-1) can exploit this mode of spread. Receptor recognition by HIV-1 occurs via interactions between the viral surface envelope glycoprotein (Env), gp120, and CD4 and a chemokine receptor, CCR5 or CXCR4. Here, we demonstrate that the binding of CXCR4-using HIV-1–infected effector T cells to primary CD4+/CXCR4+ target T cells results in rapid recruitment to the interface of CD4, CXCR4, talin, and lymphocyte function–associated antigen 1 on the target cell, and of Env and Gag on the effector cell. Recruitment of these membrane molecules into polarized clusters was dependent on Env engagement of CD4 and CXCR4 and required remodelling of the actin cytoskeleton. Transfer of Gag from effector to target cell was observed by 1 h after conjugate formation, was independent of cell–cell fusion, and was probably mediated by directed virion fusion with the target cell. We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell.

Key Words: CD4 • CXCR4 • cytoskeleton • T cells • adhesion molecules

Abbreviations used in this paper: BDM, butane-dione monoxime; CKR, chemokine receptor; Env, envelope glycoprotein; RT, room temperature; TEM, transmission electron microscopy; WB, wash buffer.


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