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. [Display omitted] •Astrocytes may endocytose virions from cell-free or cell-cell sources•HIV-1 virions do not fuse with astrocytes and astrocytes are not infected•Astrocytes cluster with HIV-1-infected macrophages•Astrocytes engulf macrophage material, including HIV-1-infected debris HIV-1 disseminates to diverse tissues and establishes long-lived viral reservoirs. These reservoirs include macrophage-lineage cells in the CNS, and previous studies indicate that astrocytes may be infected. Russell et al. find that astrocytes are not infected by virus but can engulf macrophage material, including HIV-1-infected debris.