title: Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.
abstract: Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Department of Medicine, Université de Montréal, Montreal, Quebec, H2X 0A9, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, Quebec, H2X 0A9, Canada.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Baxter
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Russell
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Moore
authors.affiliation: The Weatherall Institute of Molecular Medicine, The Nuffield Department of Medicine, The University of Oxford, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Willberg
authors.affiliation: Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Pablos
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, Quebec, H2X 0A9, Canada; Department of Microbiology, Infection and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: Department of Medicine, Université de Montréal, Montreal, Quebec, H2X 0A9, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, Quebec, H2X 0A9, Canada; The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02114, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Fedde
authors.initials: F
authors.lastname: Groot
authors.affiliation: The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: quentin.sattentau@path.ox.ac.uk.
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D015728:Receptors, HIV / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D056189:Viral Tropism
chemical_list: D015728:Receptors, HIV; D014759:Viral Envelope Proteins