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 central nervous system (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 central nervous system, viral reservoir formation and antiretroviral therapy