High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner

• Published in: Journal of colloid and interface science Vol. 645; pp. 627 - 638
• Main Authors: Correa, Yubexi, Del Giudice, Rita, Waldie, Sarah, Thépaut, Michel, Micciula, Samantha, Gerelli, Yuri, Moulin, Martine, Delaunay, Clara, Fieschi, Franck, Pichler, Harald, Haertlein, Michael, Forsyth, V. Trevor, Le Brun, Anton, Moir, Michael, Russell, Robert A., Darwish, Tamim, Brinck, Jonas, Wodaje, Tigist, Jansen, Martin, Martín, César, Roosen - Runge, Felix, Cárdenas, Marité
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2023; Elsevier; Published by Elsevier Inc
• Subjects: Basic Medicine; Cholesterol; Cholesterol efflux capacity; COVID-19; Deuterated cholesterol; HDL; Humans; Life Sciences; Lipid metabolism; Lipids; Lipoproteins, HDL; Läkemedelskemi; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinal Chemistry; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Neutron reflection; SARS-CoV-2; SARS-CoV-2 - metabolism; SARS-CoV-2 spike protein; Spike Glycoprotein, Coronavirus; Triglycerides; 50 mM Tris buffer; MCMC; SLD; Neutron reflection; h-TBS; COVID-19; CARC; HDL-C; BSA; Lipid metabolism; DMPC; CEC; CmSi; LTHC; DC assay; SDS; HTHC; Cholesterol efflux capacity; d-TBS; SLBs; EGTA; m-RNA; NaCl; d-DMPC; RCT; NR; Deuterated cholesterol; ATR-FTIR; LDL-C; Lipids; DLS; ACAT; CRAC; HDL; SARS-CoV-2 spike protein; NaF; LDL; CaCl2; d-cholesterol; LTLC; NaP; S protein; Peek; SR-B1; EDTA; TC; TG; ApoA-I; d-PLPC; PL
• ISSN: 0021-9797; 1095-7103; 1095-7103
• DOI: 10.1016/j.jcis.2023.04.137

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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.