Dynamics of HIV-Containing Compartments in Macrophages Reveal Sequestration of Virions and Transient Surface Connections

International audience; During HIV pathogenesis, infected macrophages behave as ‘‘viral reservoirs’’ that accumulate and retain virions withindedicated internal Virus-Containing Compartments (VCCs). The nature of VCCs remains ill characterized and controversial.Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed thebiogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral proteinsynthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packedand immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in theirlumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to Tcells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions intodense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, livecell imaging combined with correlative light and electron microscopy revealed that such connections can be transient,highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some ofits macrophage specific features