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Cell Host Microbe. 2014 Dec 10;16(6):711-21. doi: 10.1016/j.chom.2014.10.010. Epub 2014 Nov 20.

Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

Author information

1
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.
2
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
3
The Weatherall Institute of Molecular Medicine, The Nuffield Department of Medicine, The University of Oxford, Headley Way, Oxford OX3 9DU, UK.
4
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain.
5
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.
6
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.
7
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
8
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.

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.

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PMID:
25467409
PMCID:
PMC4271767
DOI:
10.1016/j.chom.2014.10.010
[Indexed for MEDLINE]
Free PMC Article

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