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High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner.
Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).ORCID iD: 0000-0002-9927-9413
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Life Sciences Group, Institut Laue Langevin, Grenoble F-38042, France; Partnership for Structural Biology, Grenoble F-38042, France.ORCID iD: 0000-0003-3458-887X
Univ. Grenoble Alpes, CNRS, CEA, IBS, 71 avenue des Martyrs, F-38000 Grenoble, France.
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2023 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 645, p. 627-638, article id S0021-9797(23)00736-1Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 645, p. 627-638, article id S0021-9797(23)00736-1
Keywords [en]
COVID-19, Cholesterol efflux capacity, Deuterated cholesterol, HDL, Lipid metabolism, Lipids, Neutron reflection, SARS-CoV-2 spike protein
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:mau:diva-61402DOI: 10.1016/j.jcis.2023.04.137ISI: 001004237100001PubMedID: 37167912Scopus ID: 2-s2.0-85158888783OAI: oai:DiVA.org:mau-61402DiVA, id: diva2:1774928
Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2024-04-04Bibliographically approved
In thesis
1. Role of lipoprotein structure and dynamics in disease development: from atherosclerosis to Covid-19
Open this publication in new window or tab >>Role of lipoprotein structure and dynamics in disease development: from atherosclerosis to Covid-19
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such as cholesterol and triglycerides in the bloodstream. Atherosclerosis is a complex cardiovascular disease characterized by the accumulation of cholesterol-rich plaques in arterial walls, leading to narrowed and hardened arteries. Recently, the spike protein from the SARS-CoV-2 virus, responsible for COVID-19, has been the subject of research concerning its potential impact on lipid metabolism and its association with cardiovascular disease. Understanding the interaction between lipoproteins and the spike protein influence on lipid metabolism could have implications for our knowledge of cardiovascular health.

In this research, we investigated the ultrastructure of HDL from individuals with different lipid profiles as well as the interaction of mature HDL and model of nascent HDL with model membranes. Understanding these differences will help create novel rHDL particles with superior lipid-removing and CVD-treating properties. Finally, the interaction between the spike protein and HDL in model cell membranes to study potential imbalances in lipid metabolism. To achieve the different objectives, lipid deposition, exchange and removal were followed by techniques such as Neutron reflection and attenuated total reflection Fourier transformation infrared spectroscopy while, the ultrastructure was unravelled by small-angle X-ray scattering.

Abstract [es]

En la sangre humana, las lipoproteínas sirven como transportador de lípidos como el colesterol y los triglicéridos. Cuando se acumula demasiado colesterol en las arterias, puede causar aterosclerosis, una condición que puede afectar al corazón.

Ahora se ha hablado mucho sobre la proteína “spike” del virus que causó la pandemia de COVID-19. Los investigadores encuentran una conexión entre cómo el virus y esta proteína en particular podrían afectar la forma en que el cuerpo humano maneja las grasas. Esto es importante porque podría mostrar una relación entre la enfermedad causada por este virus y las enfermedades cardiovasculares.

En esta tesis, analicé de cerca la estructura del HDL, el tipo de lipoproteína también conocida como “colesterol bueno”. Correlacioné su estructura con cómo el HDL intercambia grasas de Membranas Celulares modelo, que consisten en un modelo simplificado de las paredes de nuestras células. Mi intención era descubrir estas correlaciones porque podrían ayudarnos a producir HDL artificiales que pueden ser usadas para eliminar grasas y tratar problemas cardíacos.

Por último, observé cómo se comporta la proteína “spike” del virus que causa la enfermedad COVID-19 y el HDL cuando se encuentran juntos en las paredes celulares modelo. Esto podría decirnos si esta proteína afecta como nuestro cuerpo maneja la grasa.

Para estudiar todo esto, utilicé algunas técnicas sofisticadas como la reflexión de neutrones y la espectroscopia infrarroja para rastrear cómo se mueven las grasas, y también rayos X para tomar "fotografías" de la estructura del HDL. 

Abstract [sv]

I mänskligt blod arbetar lipoproteiner som viktiga bärare av fetter som kolesterol och triglycerider. När för mycket kolesterol ansamlas i artärerna kan det orsaka ateroskleros, ett sjukdomstillstånd som påverkar hjärtat.

De senaste åren har det varit mycket diskussioner om "spike-proteinet" från det virus som orsakade COVID-19 pandemin. Forskare har funnit ett samband mellan hur viruset och detta protein kan påverka hur den mänskliga kroppen hanterar fett. Detta skulle kunna vara viktigt eftersom det kan visa på ett samband mellan sjukdomen orsakad av viruset och hjärt-kärlsjukdomar. I denna avhandling har jag tittat närmare på strukturen för HDL, den typ av lipoprotein som är känd som "det goda kolesterolet". Jag korrelerade dess struktur med hur HDL utbyter fett från modellmembran, en förenklad modell av våra cellväggar. Jag hade för avsikt att utreda dessa korrelationer eftersom de skulle kunna hjälpa oss att skapa skräddarskydd HDL som är ännu bättre på att avlägsna fett och behandla hjärt-kärlsjukdom.

Slutligen tittade jag på hur "spike-proteinet" från viruset som orsakade COVID19 och HDL uppför sig när de möts vid ett modellmembran. Detta skulle kunna berätta för oss huruvida detta protein påverkar hur våra kroppar hanterar fett.

För att undersöka allt detta har jag använt tjusiga metoder som neutronreflektion och infraröd spektroskopi för att spåra hur fett rör sig och röntgen för att ta "bilder" på HDLs struktur. 

Place, publisher, year, edition, pages
Malmö: Malmö University Press, 2023. p. 83
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 6
National Category
Cardiac and Cardiovascular Systems
Research subject
Health and society
Identifiers
urn:nbn:se:mau:diva-64195 (URN)10.24834/isbn.9789178773978 (DOI)978-91-7877-396-1 (ISBN)978-91-7877-397-8 (ISBN)
Public defence
2023-11-24, E002, Jan Waldenströms gata 25, Malmö, 13:00 (English)
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Supervisors
Note

Paper I and II in dissertation as manuscript

Available from: 2023-12-11 Created: 2023-12-10 Last updated: 2024-02-29Bibliographically approved

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Correa, YubexiDel Giudice, RitaWaldie, SarahRoosen-Runge, FelixCárdenas, Marité

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