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Cell Rep. 2017 Feb 7;18(6):1473-1483. doi: 10.1016/j.celrep.2017.01.027.

Astrocytes Resist HIV-1 Fusion but Engulf Infected Macrophage Material.

Author information

1
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
2
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
3
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK; Wellcome Trust Centre for Human Genetics, Cellular Imaging Core, University of Oxford, Oxford OX3 7BN, UK.
4
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
5
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. Electronic address: quentin.sattentau@path.ox.ac.uk.

Abstract

HIV-1 disseminates to diverse tissues and establishes long-lived viral reservoirs. These reservoirs include the CNS, in which macrophage-lineage cells, and as suggested by many studies, astrocytes, may be infected. Here, we have investigated astrocyte infection by HIV-1. We confirm that astrocytes trap and internalize HIV-1 particles for subsequent release but find no evidence that these particles infect the cell. Astrocyte infection was not observed by cell-free or cell-to-cell routes using diverse approaches, including luciferase and GFP reporter viruses, fixed and live-cell fusion assays, multispectral flow cytometry, and super-resolution imaging. By contrast, we observed intimate interactions between HIV-1-infected macrophages and astrocytes leading to signals that might be mistaken for astrocyte infection using less stringent approaches. These results have implications for HIV-1 infection of the CNS, viral reservoir formation, and antiretroviral therapy.

KEYWORDS:

HIV-1; astrocyte; brain; fusion; macrophage; phagocytosis

PMID:
28178524
PMCID:
PMC5316642
DOI:
10.1016/j.celrep.2017.01.027
[Indexed for MEDLINE]
Free PMC Article

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