CXCR4 is a functional coreceptor for infection of human macrophages by CXCR4-dependent primary HIV-1 isolates. 1998

A Verani, and E Pesenti, and S Polo, and E Tresoldi, and G Scarlatti, and P Lusso, and A G Siccardi, and D Vercelli
Unit of Molecular Immunoregulation, San Raffaele Scientific Institute, Milan, Italy.

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.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D016176 T-Lymphocyte Subsets A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells. T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets
D054377 Chemokine CXCL12 A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing. CXCL12 Chemokine,Stromal Cell-Derived Factor-1beta,Chemokine (C-X-C Motif) Ligand 12,Pre-B-Cell Growth-Stimulating Factor,SDF-1alpha,SDF-1beta,SDF1-3'A,Stromal Cell-Derived Factor 1,Stromal Cell-Derived Factor-1alpha,CXCL12, Chemokine,Cell-Derived Factor-1beta, Stromal,Chemokine, CXCL12,Growth-Stimulating Factor, Pre-B-Cell,Pre B Cell Growth Stimulating Factor,SDF 1alpha,SDF 1beta,SDF1 3'A,Stromal Cell Derived Factor 1,Stromal Cell Derived Factor 1alpha,Stromal Cell Derived Factor 1beta
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D019718 Receptors, CXCR4 CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS. CXC Chemokine Receptor 4,CXCR4 Receptors,Fusin,CXCR4 Receptor,LESTR Receptor,Leukocyte-Derived Seven-Transmembrane Domain Receptor,Receptor, LESTR,Leukocyte Derived Seven Transmembrane Domain Receptor,Receptor, CXCR4
D019743 Chemokines, CXC Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes. C-X-C Chemokine,CXC Chemokine,CXC Chemokines,alpha-Chemokine,alpha-Chemokines,C-X-C Chemokines,C X C Chemokine,Chemokine, C-X-C,Chemokine, CXC,Chemokines, C-X-C,alpha Chemokine,alpha Chemokines

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