The Journal of Experimental Medicine
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J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2433/06 $2.00
Volume 184 December 1996 2433-2438

BRIEF DEFINITIVE REPORT:
Efficient Interaction of HIV-1 with Purified Dendritic Cells via Multiple Chemokine Coreceptors

By Angela Granelli-Piperno,par Bernhard Moser,* Melissa Pope,par Dongling Chen,par Yang Wei,par Frank Isdell,par Una O'Doherty,par William Paxton,Dagger Richard Koup,Dagger Svetlana Mojsov,par Nina Bhardwaj,par Ian Clark-Lewis,§ Marco Baggiolini,* and Ralph M. Steinmanpar

From the * Theodor Kocher Institute, Bern CH-3000, Switzerland; Dagger  Aaron Diamond AIDS Research Center, New York 10016; § Biomedical Research Center, University of British Columbia, Vancouver, British Columbia V6T-2Z3, Canada; and par  Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021

HIV-1 actively replicates in dendritic cell (DC)-T cell cocultures, but it has been difficult to demonstrate substantial infection of purified mature DCs. We now find that HIV-1 begins reverse transcription much more efficiently in DCs than T cells, even though T cells have higher levels of CD4 and gp120 binding. DCs isolated from skin or from blood precursors behave similarly. Several M-tropic strains and the T-tropic strain IIIB enter DCs efficiently, as assessed by the progressive formation of the early products of reverse transcription after a 90-min virus pulse at 37°C. However, few late gag-containing sequences are detected, so that active viral replication does not occur. The formation of these early transcripts seems to follow entry of HIV-1, rather than binding of virions that contain viral DNA. Early transcripts are scarce if DCs are exposed to virus on ice for 4 h, or for 90 min at 37°C, conditions which allow virus binding. Also the early transcripts once formed are insensitive to trypsin. The entry of a M-tropic isolates is blocked by the chemokine RANTES, and the entry of IIIB by SDF-1. RANTES interacts with CCR5 and SDF-1 with CXCR4 receptors. Entry of M-tropic but not T-tropic virus is ablated in DCs from individuals who lack a functional CCR5 receptor. DCs express more CCR5 and CXCR4 mRNA than T cells. Therefore, while HIV-1 does not replicate efficiently in mature DCs, viral entry can be active and can be blocked by chemokines that act on known receptors for M- and T-tropic virus.


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