Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors.
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.
Granelli-Piperno
A
A
Theodor Kocher Institute, Bern, Switzerland.
Moser
B
B
Pope
M
M
Chen
D
D
Wei
Y
Y
Isdell
F
F
O'Doherty
U
U
Paxton
W
W
Koup
R
R
Mojsov
S
S
Bhardwaj
N
N
Clark-Lewis
I
I
Baggiolini
M
M
Steinman
R M
RM
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
D018946:Chemokine CCL5; D015683:Gene Products, gag; D018121:Receptors, Cytokine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor