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A strategy adopted to combat human immunodeficiency virus type-1 (HIV-1) infection is based on interfering with virus entry into target cells. In this study, we found that phosphatidylcholine (PC) liposomes reduced the expression of the CD4 receptor in human primary type-1 macrophages but not in CD4+ T cells. The down-regulation was specific to CD4, as any effect was not observed in CCR5 membrane expression. Moreover, the reduction of membrane CD4 expression required the Ca2+-independent protein kinase C (PKC), which in turn mediated serine phosphorylation in the intracytoplasmic tail of the CD4 receptor. Serine phosphorylation of CD4 was also associated with its internalization and degradation in acidic compartments. Finally, the observed CD4 downregulation induced by PC liposomes in human primary macrophages reduced the entry of both single-cycle replication and replication competent R5 tropic HIV-1. Altogether, these results show that PC liposomes reduce HIV entry in human macrophages and may impact HIV pathogenesis by lowering the viral reservoir. Copyright © 2022 De Santis, Lopez, Virtuoso, Poerio, Saccomandi, Olimpieri, Duca, Henrici De Angelis, Aquilano, D’Andrea, Aquaro, Borsetti, Ceccherini-Silberstein and Fraziano.


Federica De Santis, Ana Borrajo Lopez, Sara Virtuoso, Noemi Poerio, Patrizia Saccomandi, Tommaso Olimpieri, Leonardo Duca, Lucia Henrici De Angelis, Katia Aquilano, Marco Maria D'Andrea, Stefano Aquaro, Alessandra Borsetti, Francesca Ceccherini-Silberstein, Maurizio Fraziano. Phosphatidylcholine Liposomes Down-Modulate CD4 Expression Reducing HIV Entry in Human Type-1 Macrophages. Frontiers in immunology. 2022;13:830788

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PMID: 35663973

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