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°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°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.

Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation

“…Broadly similar results have been described for CD34 + cell-derived DC [27] as well as responses to C5a in Langerhans cells [28]. Chemokine receptors on DC are now being characterized [25,[29][30][31]. Of particular interest are CCR5 which binds MIP-1 § , MIP-1 g and RANTES, and CXCR4 which binds SDF-1, both of which are co-receptors for HIV-1 [32].…”

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

“…Increased susceptibility due to BV may occur through few mechanisms. First, mature dendritic induce more efficient T-cell activation leading to increased HIV infection of T cells [60] and second, direct DC infection and DC-mediated trans-infection of HIV can also be affected by the maturation state of DC [61,62]. Langerhans Cells (LC), which are a subtype of DC found in tissues, have increased HIV uptake after stimulation [63].…”

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

“…Peripheral blood mononuclear cells (PBMC) of rhesus macaque (Macaca mulatta) were Ficoll gradient-purified from peripheral blood and cultured in the presence of 500 units͞ml IL-4 and 800 units͞ml granulocytemacrophage colony-stimulating factor (R & D Systems). Total RNA was isolated from the cultured cells with Trizol (Life Technologies, Grand Island, NY), primed with oligo(dT) [12][13][14][15][16][17][18] , and transcribed by using Superscript II reverse transcriptase (Life Technologies) according to the manufacturer's protocol. mac-DC-SIGN cDNA was amplified with the following primers: dc-sign1, 5Ј-AGT GGG GTG ACA TGA GTG AC-3Ј and s-9m, 5Ј-GAA GTT CTG CTA CTC AGG AG-3Ј.…”