Macrophage Infection via Selective Capture of HIV-1-Infected CD4+ T Cells

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. [Display omitted] •Macrophages selectively capture and engulf HIV-1-infected T cells•Uptake of HIV-1-infected T cells drives efficient macrophage infection•T cell capture is viral Env independent; macrophage infection is Env-receptor dependent•This represents a route for macrophage infection by transmitted/founder viruses Tissue macrophages play an important role in HIV-1 infection as viral reservoirs. Baxter et al find that engulfment of HIV-1-infected T cells represents an efficient route by which macrophages may become infected. This mode of spread enables weakly macrophage-tropic transmitted/founder viruses, implicated in viral transmission, to infect macrophages.