Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4⁺ T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. • HIV-1-infected T cells form viral synapse with the epithelium in reconstructed mucosa • These viral synapse dynamics were recorded by live imaging for the first time • HIV-1 formed at the viral synapse crosses the epithelium by transcytosis • Transcytosed HIV-1 targets stromal macrophages, resulting in their latent infection Real et al. established by live imaging the dynamics of virological synapses formed between HIV-1-infected T cells and the epithelium at the surface of a human reconstructed mucosa. HIV-1 virions formed at the viral synapse cross the epithelium and reach the mucosal stroma, where the virus establishes a latent infection in macrophages. [ABSTRACT FROM AUTHOR]