Macrophage infection by fusion with HIV-1-infected T lymphocytes: Catch me to fuse
Although antiretroviral therapies are effective in reducing viral load in HIV-1 infected patients, one of the major challenges to complete eradication of the virus remains the elimination of viral reservoirs. Along with CD4 T cells, macrophages are main targets of HIV-1. Infected macrophages participate in disease progression and persistence of cellular reservoirs. It is therefore essential to better understand how macrophages are infected. The work of the researchers, published in The Journal of Cell Biology, proposes that the intercellular transmission of the virus from infected T lymphocytes to macrophages through a fusion mechanism between the two cell types constitutes the major mode of macrophage infection in vivo.
The researchers showed that the mechanism of fusion of macrophages with HIV-1-infected T cells is the most rapid and efficient way of virus propagation in vitro. This mode of transmission also allows for efficient infection of human resident macrophages from several tissues, including alveolar macrophages of the lung. The ability of macrophages to be infected by this mechanism is modulated by the activation state of the macrophages, and is strongly inhibited in pro-inflammatory contexts. At the molecular level, the scientists showed that this infection through heterotypic fusion engages a specific short-lived adhesion structure where F-actin and beta-2 integrins accumulate. It is regulated by the tetraspanin membrane protein CD81, which initiates a signaling cascade, resulting in a strong cortical network unfavorable to fusion between the two cell types.
This study highlights the importance and the mechanisms of tissue macrophage infection, and may lead to develop new strategies to eradicate persistent cellular reservoirs in patients.
Specific adhesion between an HIV-1-infected T lymphocyte (pink) and a macrophage (grey) before fusion of the two cells – Scanning electron microscopy, Credit Renaud Poincloux/Rémi Mascarau
Source
Rémi Mascarau1-2, Marie Woottum3,#, Léa Fromont1,#, Rémi Gence4, Vincent Cantaloube-Ferrieu5, Zoï Vahlas1-2, Kevin Lévêque1, Florent Bertrand1, Thomas Beunon1, Arnaud Métais1, , Hicham El Costa5, Nabila Jabrane-Ferrat5, Yohan Gallois6, Nicolas Guibert7, Jean-Luc Davignon8, Gilles Favre4, Isabelle Maridonneau-Parini1,2, Renaud Poincloux1-2, Bernard Lagane5, Serge Bénichou3, Brigitte Raynaud-Messina1-2, *¶ and Christel Vérollet1-2, *¶. Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells. J Cell Biol (2023) 222 (5): e202205103. https://doi.org/10.1083/jcb.202205103.
Contact
Brigitte Raynaud-Messina (raynaud@ipbs.fr) and Christel Vérollet (verollet@ipbs.fr)
Press contact
Françoise Viala (communication@ipbs.fr)