The influence of cytokines, chemokines and their receptors on HIV‐1 replication in monocytes and macrophages

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Abstract
Monocytes, macrophages and dendritic cells play an important role in the initial infection and contribute to its pathogenesis throughout the course of infection. Myeloid cells express CD4 and chemokine receptors known for HIV‐1 fusion and entry. The β‐chemokine receptor, CCR5, is the major co‐receptor in conjunction with CD4 for macrophage (M)‐tropic or (R5) isolates of HIV‐1, whereas the α‐chemokine receptor, CXCR4, facilitates entry of T‐tropic or (X4) HIV‐1 strains. Cells of myeloid lineage may be infected predominantly with R5‐ strains, although infection with dual‐tropic isolates of HIV‐1 (exhibiting the capacity to use CCR‐5 and/or CXCR‐4 for entry) or some strains of X4‐ isolates has also been reported. The expression of chemokine receptors, HIV‐1 infectio n and replication is under continuous regulation by a complex cytokine network produced by a variety of cells. The effects of cytokines/chemokines on HIV‐1 replication in cells of myeloid lineage can be inhibitory (IFN‐α, IFN‐β, IFN‐γ, GM‐CSF, IL‐10, IL‐13 and IL‐16 and β‐chemok ines), stimulatory (M‐CSF, TNF‐α, TNF‐β, IL‐1, IL‐6) or bifunction al, that is both inhibitory and stimulatory (IL‐4). This review focuses on the overall expression of chemokine receptors on cells of myeloid lineage and considers the mechanisms of entry of R5‐, X4‐ and dual‐tropic strains of HIV‐1 into these cells. The effects of cytokines/chemokines on viral entry and productive HIV‐1 infection are also reviewed. Copyright © 2003 John Wiley & Sons, Ltd.

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