Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors

• Published in: The Journal of experimental medicine 1996-12, Vol.184 (6), p.2433-2438
• Main Authors: Granelli-Piperno, A, Moser, B, Pope, M, Chen, D, Wei, Y, Isdell, F, O'Doherty, U, Paxton, W, Koup, R, Mojsov, S, Bhardwaj, N, Clark-Lewis, I, Baggiolini, M, Steinman, R M
• Format: Article
• Language: English
• Subjects: Brief Definitive Report; Cells, Cultured; Chemokine CCL5 - pharmacology; Coculture Techniques; Dendritic Cells - immunology; Dendritic Cells - virology; Gene Products, gag - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; HIV-1 - drug effects; HIV-1 - immunology; HIV-1 - physiology; human immunodeficiency virus 1; Humans; Interleukin-4 - pharmacology; Polymerase Chain Reaction; Receptors, Cytokine - immunology; Skin - immunology; T-Lymphocytes - immunology; T-Lymphocytes - virology; Transcription, Genetic; Virion - immunology; Virion - physiology; Virus Replication
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.184.6.2433

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 known receptors for M- and T-tropic virus.