CXCR4 is a functional coreceptor for infection of human macrophages by CXCR4-dependent primary HIV-1 isolates.
The identification of HIV-1 coreceptors has provided a molecular basis for the tropism of different HIV-1 strains. CXC chemokine receptor-4 (CXCR4) mediates the entry of both primary and T cell line-adapted (TCLA) syncytia-inducing strains. Although macrophages (M phi) express CXCR4, this coreceptor is assumed to be nonfunctional for HIV-1 infection. We addressed this apparent paradox by infecting human monocyte-derived M phi with primary and TCLA isolates that were rigorously characterized for coreceptor usage and by adding the natural CXCR4 ligand, stem cell differentiation factor-1, to specifically block CXCR4-mediated entry. Our results show that primary HIV-1 isolates that selectively use CXCR4 productively infected both normal and C-C chemokine receptor-5-null M phi. By contrast, M phi supported the entry of CXCR4-dependent TCLA strains with variable efficiency but were not productively infected. Thus, the tropism of HIV isolates results from complex virus/host cell interactions both at the entry and postentry levels.
Verani
A
A
Unit of Molecular Immunoregulation, San Raffaele Scientific Institute, Milan, Italy.
Pesenti
E
E
Polo
S
S
Tresoldi
E
E
Scarlatti
G
G
Lusso
P
P
Siccardi
A G
AG
Vercelli
D
D
D019380:Anti-HIV Agents / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4