Efficient Interaction of HIV-1 with Purified Dendritic Cells via Multiple Chemokine Coreceptors
Autor: | Nina Bhardwaj, Marco Baggiolini, Ralph M. Steinman, Yang Wei, Melissa Pope, Frank Isdell, Svetlana Mojsov, Dongling Chen, William A. Paxton, Ian Clark-Lewis, Una O'Doherty, Bernhard Moser, Richard A. Koup, Angela Granelli-Piperno |
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Přispěvatelé: | Other departments |
Rok vydání: | 1996 |
Předmět: |
Chemokine
Transcription Genetic Chemokine receptor CCR5 T-Lymphocytes viruses Immunology Gene Products gag Virus Replication Polymerase Chain Reaction Virus 03 medical and health sciences Chemokine receptor 0302 clinical medicine Viral entry Humans Immunology and Allergy Receptors Cytokine Chemokine CCL5 Cells Cultured Interleukin 4 Skin 030304 developmental biology 0303 health sciences biology Virion Brief Definitive Report Granulocyte-Macrophage Colony-Stimulating Factor virus diseases Dendritic Cells Dendritic cell Virology Coculture Techniques 3. Good health Viral replication HIV-1 biology.protein Brief Definitive Reports Interleukin-4 030215 immunology |
Zdroj: | The Journal of Experimental Medicine Journal of experimental medicine, 184(6), 2433-2438. Rockefeller University Press |
ISSN: | 1540-9538 0022-1007 |
Popis: | 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. |
Databáze: | OpenAIRE |
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