LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes


Baptiste Pradel, Guilhem Cantaloube, Marie Villares, Maïka S Deffieu, Véronique Robert-Hebmann, Vincent Lucansky, Mathias Faure, Nathalie Chazal, Raphaël Gaudin, Lucile Espert.

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HIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure leads to the rapid LC3B enrichment toward the target cell plasma membrane, in close proximity with the incoming viral particles. Furthermore, we demonstrated that Atg8ylation is a key event facilitating HIV-1 entry in target CD4+ T cells. Interestingly, this effect is independent of canonical autophagy as ATG13 silencing does not prevent HIV-1 entry. Together, our results provide an unconventional role of LC3B conjugation subverted by HIV-1 to achieve a critical step of its replication cycle.

Graphical abstract

LC3B puncta are enriched toward the target cell PM, near the incoming viruses