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

• Published in: Autophagy Vol. 20; no. 8; pp. 1825 - 1836
• Main Authors: Pradel, Baptiste, Cantaloube, Guilhem, Villares, Marie, Deffieu, Maïka S, Robert-Hebmann, Véronique, Lucansky, Vincent, Faure, Mathias, Chazal, Nathalie, Gaudin, Raphaël, Espert, Lucile
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02-08-2024
• Subjects: Autophagy - physiology; Autophagy-Related Protein 8 Family - metabolism; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cell Membrane - metabolism; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - metabolism; HIV-1 - physiology; Humans; Life Sciences; Microtubule-Associated Proteins - metabolism; Virus Internalization; Virus Replication - physiology; HIV-1; virus entry; Atg8ylation; CD4+ T lymphocyte; LC3B; CD4 + T lymphocyte
• ISSN: 1554-8627; 1554-8635; 1554-8635
• DOI: 10.1080/15548627.2024.2338573

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.
: BafA1: bafilomycin A1; BlaM: beta-lactamase; CD4
TL: CD4
T lymphocytes; PtdIns3K-BECN1 complex: BECN1-containing class III phosphatidylinositol 3-kinase complex; Env: HIV-1 envelope glycoproteins; HIV-1: type 1 human immunodeficiency virus; PM: plasma membrane; PtdIns3P: phosphatidylinositol-3-phosphate; VLP: virus-like particle.