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Article Dans Une Revue Journal of Cell Biology Année : 2023

Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells

Marie Woottum
Jean-Luc Davignon
Serge Bénichou

Résumé

Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.
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hal-04087834 , version 1 (03-05-2023)

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Rémi Mascarau, Marie Woottum, Léa Fromont, Rémi Gence, Vincent Cantaloube-Ferrieu, et al.. Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells. Journal of Cell Biology, 2023, Immune Cell Biology 2023, 222 (5), ⟨10.1083/jcb.202205103⟩. ⟨hal-04087834⟩
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