EFFICIENT INTERACTION OF HIV-1 WITH PURIFIED DENDRITIC CELLS VIA MULTIPLE CHEMOKINE CORECEPTORS

HIV-1 actively replicates in dendritic cell (DC)-T cell cocultures, bu t it has been difficult to demonstrate substantial infection of purifi ed mature DCs. We now find that HIV-1 begins reverse transcription muc h more efficiently in DCs than T cells, even though T cells have highe r levels of CD4 and gp120 binding. DCs isolated from skin or from bloo d precursors behave similarly. Several M-tropic strains and the T-trop ic strain IIIB enter DCs efficiently, as assessed by the progressive f ormation of the early products of reverse transcription after a 90-min virus pulse at 37 degrees C. However, few late gag-containing sequenc es are detected, so that active viral replication does not occur. The formation of these early transcripts seems to follow entry of HIV-1, r ather than binding of virions that contain viral DNA. Early transcript s are scarce if DCs are exposed to virus on ice for 4 h, or for 90 min at 37 degrees 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 I IIB by SDF-1. RANTES interacts with CCR5 and SDF-1 with CXCR4 receptor s. Entry of M-tropic but not T-tropic virus is ablated in DCs from ind ividuals who lack a functional CCR5 receptor. DCs express more CCR5 an d CXCR4 mRNA than T cells. Therefore, while HIV-1 does not replicate e fficiently 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.