RT Journal Article
T1 The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane
A1 Py, Bénédicte
A1 Basmaciogullari, Stéphane
A1 Bouchet, Jérôme
A1 Zarka, Marion
A1 Moura, Ivan
A1 Benhamou, Marc
A1 Monteiro, Renato
A1 Hocini, Hakim
A1 Madrid González, Ricardo
A1 Benichou, Serge
AB Secretory leukocyte protease inhibitor (SLPI) is secreted by epithelial cells in all the mucosal fluids such as saliva, cervical mucus, as well in the seminal liquid. At the physiological concentrations found in saliva, SLPI has a specific antiviral activity against HIV-1 that is related to the perturbation of the virus entry process at a stage posterior to the interaction of the viral surface glycoprotein with the CD4 receptor. Here, we confirm that recombinant SLPI is able to inhibit HIV-1 infection of primary T lymphocytes, and show that SLPI can also inhibit the transfer of HIV-1 virions from primary monocyte-derived dendritic cells to autologous T lymphocytes. At the molecular level, we show that SLPI is a ligand for the phospholipid scramblase 1 (PLSCR1) and PLSCR4, membrane proteins that are involved in the regulation of the movements of phospholipids between the inner and outer leaflets of the plasma membrane. Interestingly, we reveal that PLSCR1 and PLSCR4 also interact directly with the CD4 receptor at the cell surface of T lymphocytes. We find that the same region of the cytoplasmic domain of PLSCR1 is involved in the binding to CD4 and SLPI. Since SLPI was able to disrupt the association between PLSCR1 and CD4, our data suggest that SLPI inhibits HIV-1 infection by modulating the interaction of the CD4 receptor with PLSCRs. These interactions may constitute new targets for antiviral intervention
SN 1932-6203
YR 2009
FD 2009
LK https://hdl.handle.net/20.500.14352/98313
UL https://hdl.handle.net/20.500.14352/98313
LA eng
NO Py B, Basmaciogullari S, Bouchet J, Zarka M, Moura IC, Benhamou M, et al. (2009) The Phospholipid Scramblases 1 and 4 Are Cellular Receptors for the Secretory Leukocyte Protease Inhibitor and Interact with CD4 at the Plasma Membrane. PLoS ONE 4(3): e5006. https://doi.org/10.1371/journal.pone.0005006
DS Docta Complutense
RD 10 abr 2025