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© The Rockefeller University Press, 0022-1007/1996/12/2433/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2433-2438

Brief Definitive Reports

Efficient Interaction of HIV-1 with Purified Dendritic Cells via Multiple Chemokine Coreceptors

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

From the * Theodor Kocher Institute, Bern CH-3000, Switzerland; {ddagger} Aaron Diamond AIDS Research Center, New York 10016; § Biomedical Research Center, University of British Columbia, Vancouver, British Columbia V6T-2Z3, Canada; and || 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.

Address correspondence to Angela Granelli-Piperno, Laboratory of Cellular Physiology and Immunology, Rockefeller University, 1230 York Ave., New York, NY 10021.

Richard Koup is an Elizabeth Glaser Scientist of the Pediatric AIDS Foundation.

This work was supported by grants AI24775 and AI40045 from the NIAID, the Dorothy Schiff Foundation, and Direct Effect to R.M. Steinman, and by grant GM 50969 to I. Clark-Lewis and SNSF 31-9744.93 to M. Baggiolini and B. Moser.


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