Astrocytes Resist HIV-1 Fusion but Engulf Infected Macrophage Material.
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.
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Rebecca A
RA
Russell
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Jakub
J
Chojnacki
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.
Daniel M
DM
Jones
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Errin
E
Johnson
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Thao
T
Do
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Christian
C
Eggeling
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.
Sergi
S
Padilla-Parra
The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. Electronic address: quentin.sattentau@path.ox.ac.uk.
Quentin J
QJ
Sattentau
D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D002459:Cell Fusion / Q000379:methods; D002490:Central Nervous System / Q000378:metabolism / Q000821:virology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology*
D049452:Green Fluorescent Proteins; D008156:Luciferases
HIV-1; astrocyte; brain; fusion; macrophage; phagocytosis