Browsing by Author "Fieschi, F"

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    High-density lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
    (Elsevier B. V., 2023-09) Correa, YB; Del Giuduce, R; Waldie, S; Thépaut, M; Gerelli, Y; Moulin, M; Delauney, C; Fieschi, F; Haertlein, M; Le Brun, AP; Forsyth, VT; Moir, M; Russell, RA; Darwish, TA; Brinck, J; Wodaje, T; Jansen, M; Martín, C; Roosen-Runge, F; Cárdenas, M; Micciulla, S; Pichler, H
    There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism. © Crown Copyright 2023. Published by Elsevier Inc. Open Access - CC BY licence 4.0.
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    Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry
    (Springer Nature Limited, 2021-07-21) Luchini, A; Micciulla, S; Corucci, G; Batchu, KC; Santamaria, A; Laux, V; Darwish, TA; Russell, RA; Thépaut, M; Bally, I; Fieschi, F; Fragneto, G
    SARS-CoV-2 spike proteins are responsible for the membrane fusion event, which allows the virus to enter the host cell and cause infection. This process starts with the binding of the spike extramembrane domain to the angiotensin-converting enzyme 2 (ACE2), a membrane receptor highly abundant in the lungs. In this study, the extramembrane domain of SARS-CoV-2 Spike (sSpike) was injected on model membranes formed by supported lipid bilayers in presence and absence of the soluble part of receptor ACE2 (sACE2), and the structural features were studied at sub-nanometer level by neutron reflection. In all cases the presence of the protein produced a remarkable degradation of the lipid bilayer. Indeed, both for membranes from synthetic and natural lipids, a significant reduction of the surface coverage was observed. Quartz crystal microbalance measurements showed that lipid extraction starts immediately after sSpike protein injection. All measurements indicate that the presence of proteins induces the removal of membrane lipids, both in the presence and in the absence of ACE2, suggesting that sSpike molecules strongly associate with lipids, and strip them away from the bilayer, via a non-specific interaction. A cooperative effect of sACE2 and sSpike on lipid extraction was also observed. © 2021 The Authors CC BY 4.0