Progesterone and a phospholipase inhibitor increase the endosomal bis(monoacylglycero)phosphate content and block HIV viral particle intercellular transmission |
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| Authors: | Sabine Chapuy-Regaud,Caroline Subra,Mary Requena,Philippe de Medina,Sawsan Amara,Isabelle Delton-Vandenbroucke,Bruno Payre,Michelle Cazabat,Fré dé ric Carriere,Jacques Izopet,Marc Poirot,Michel Record |
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| Affiliation: | 1. INSERM, U1043, Equipe “Infection virales: persistance, réponse de l''hôte et physiopathologie”, Toulouse F-31300, France;2. INSERM – UMR 1037, CRCT, Equipe “Métabolisme des Stérols et Innovation Thérapeutique en Oncologie”, Toulouse F31052, France;3. Université Toulouse III Paul-Sabatier, Toulouse F-31300, France;4. CHU Toulouse, Hôpital Purpan, Laboratoire de Virologie, Toulouse F-31300, France;5. Affichem, Toulouse, France;6. CNRS, Aix-Marseille Université, Enzymologie Interfaciale et Physiologie de la Lipolyse, UMR 7282, 31 chemin Joseph Aiguier, 13402 Marseille cedex 20, France;g INSERM – UMR 1060, Equipe “Ingénierie et fonction des lipides et lipoprotéines” IMBL-Insa-Lyon, Villeurbanne F-69621, France;h Centre de Microscopie Electronique Appliquée à la Biologie, Faculté de Médecine Rangueil, F-31062 Toulouse, France |
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| Abstract: | Progesterone, the cationic amphiphile U18666A and a phospholipase inhibitor (Methyl Arachidonyl Fluoro Phosphonate, MAFP) inhibited by 70%–90% HIV production in viral reservoir cells, i.e. human THP-1 monocytes and monocyte-derived macrophages (MDM). These compounds triggered an inhibition of fluid phase endocytosis (macropinocytosis) and modified cellular lipid homeostasis since endosomes accumulated filipin-stained sterols and Bis(Monoacylglycero)Phosphate (BMP). BMP was quantified using a new cytometry procedure and was increased by 1.25 times with MAFP, 1.7 times with U18666A and 2.5 times with progesterone. MAFP but not progesterone or U18666A inhibited the hydrolysis of BMP by the Pancreatic Lipase Related Protein 2 (PLRP2) as shown by in-vitro experiments. The possible role of sterol transporters in steroid-mediated BMP increase is discussed. |
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| Keywords: | MAFP (methyl arachidonyl fluoro phosphonate) Progesterone BMP (bismonoacylglycerophosphate) Sterol transporter NPC-1 PLRP2 (pancreatic lipase-related protein 2) Desmosterol Cholesterol epoxide |
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