title: Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors.
abstract: 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.
authors.affiliation: Theodor Kocher Institute, Bern, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Granelli-Piperno
authors.forename: B
authors.initials: B
authors.lastname: Moser
authors.forename: M
authors.initials: M
authors.lastname: Pope
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: F
authors.initials: F
authors.lastname: Isdell
authors.forename: U
authors.initials: U
authors.lastname: O'Doherty
authors.forename: W
authors.initials: W
authors.lastname: Paxton
authors.forename: R
authors.initials: R
authors.lastname: Koup
authors.forename: S
authors.initials: S
authors.lastname: Mojsov
authors.forename: N
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: I
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: M
authors.initials: M
authors.lastname: Baggiolini
authors.forename: R M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000494:pharmacology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015683:Gene Products, gag / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000276:immunology*; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014158:Transcription, Genetic; D014771:Virion / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
chemical_list: D018946:Chemokine CCL5; D015683:Gene Products, gag; D018121:Receptors, Cytokine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor