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Chemokine signaling and HIV‐1 fusion mediated by macrophage CXCR4: implications for target cell tropism
Author(s) -
Collman Ronald G.,
Yi Yanjie,
Liu QingHua,
Freedman Bruce D.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.3.318
Subject(s) - biology , macrophage , chemokine , tropism , cxcr4 , chemokine receptor , cell fusion , ccr5 receptor antagonist , maraviroc , intracellular , microbiology and biotechnology , virology , cell , immunology , virus , human immunodeficiency virus (hiv) , inflammation , in vitro , genetics
To better understand CXCR4 function on macrophages and the relationship between coreceptor use and macrophage tropism among diverse HIV‐1 isolates, we analyzed macrophage pathways involved in Env‐mediated fusion, productive HIV‐1 infection, and chemokine‐elicited signaling. We found that both CXCR4 and CCR5 transduced intracellular signals in monocyte‐derived macrophages, activating K + and Cl − ion channels and elevating intracellular calcium in response to their chemokine ligands stromal cell‐derived factor‐1α and macrophage inflammatory protein‐1β, respectively. The prototype T‐tropic X4 strain IIIB infected macrophages poorly, and this was associated with failure of the IIIB Env to fuse efficiently with target macrophages despite functional CXCR4. In contrast, several primary X4 isolates mediated efficient CXCR4‐dependent fusion and productive macrophage infection. Several R5X4 strains could fuse with and infect macrophages through both CCR5 and CXCR4. Thus, macrophages express functional CXCR4 and CCR5 but primary and prototype X4 isolates differ in their ability to utilize macrophage CXCR4. Isolates classified as X4 based on coreceptor use may be phenotypically either T‐tropic or dual‐tropic and, conversely, phenotypically dual‐tropic isolates may be either R5X4 or X4 based on coreceptor use.