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

作者：Angela Granelli‐Piperno, Bernhard Moser, Melissa A. Pope, Dongliang Chen, Yang Wei, Frank Isdell, Una O’Doherty, William A. Paxton, Richard A. Koup, Svetlana Mojsov, Nina Bhardwaj, Ian Clark‐Lewis, Marco Baggiolini, Ralph M. Steinman · 发表于：The Journal of Experimental Medicine · 年份：1996 · DOI：10.1084/jem.184.6.2433 · 被引用次数：245 · 研究领域：HIV Research and Treatment、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

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 degrees 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 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 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 kno...