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Does the Sars-CoV-2 spike protein modulate High-Density Lipoprotein function?

Since the beginning of the COVID-19 outbreak in late December 2019, there has been a lot of talk about how the seriousness of the disease might be connected to the fat levels in people’s blood [1]. We were curious about how the Spike protein (S protein) from the virus interacts with High-Density Lipoproteins (HDLs), which are important for transporting cholesterol in the body [2]. In our first study [3], we discovered that the S protein removes fats from model membranes and affects HDL’s ability to deal with specific types of fats. This raised questions such as whether the S protein prefers certain fats over others and if an individual’s blood fat profile could influence how the S protein affects HDL function.

In our follow-up research [4], we tested this idea using different types of fats (saturated, monounsaturated, and polyunsaturated). We used special techniques to examine the affinities of both HDL and the S protein for these fats: in particular by using selective deuteration and neutron reflection, we could see how HDL removed and deposited fats in detail. Our findings showed that the S protein has a strong preference for saturated fats when cholesterol is present and also for polyunsaturated fats containing for example linoleic acid (Figure 1).

Next, we looked at how the mixture of fats in the blood, specifically the total amount of triglycerides and cholesterol, influences how the S protein impacts HDL function. Our findings indicate that people with a specific blood fat profile (low triglycerides and high cholesterol) might be less prone to disruptions during a COVID-19 infection or after COVID-19 vaccination. This is because, in such cases, the interaction between the S protein and HDL is not as strong (Figure 2).

These experiments were conducted in collaboration with deuteration laboratories at the ILL and ANSTO (the Australian Centre for Neutron Scattering).

We were granted beamtime at ILL on Figaro and D17, and at ANSTO on Spatz neutron reflectometers.

Y. Correa (Malmö University)

[1] R.K. Mahat, V. Rathore, N. Singh, N. Singh et al. (2021). Clin. Nutr. ESPEN, 45, 91-101.

[2] M.P. Adorni, N. Ronda, F. Bernini, F. Zimetti, (2021) Cells, 10, 574.

[3] Y. Correa, S. Waldie, M. Thépaut, S. Micciulla et al. (2021) J. Colloid Interface Sci., 602, 732-739.

[4] Y. Correa, R. Del Giudice, S. Waldie, M. Thépaut et al. (2023) J. Colloid Interface Sci., 645, 627-638.

Figures caption

Figure 1: HDL ability to remove and deposit lipids in fluid saturated membranes in the absence (A) and presence of cholesterol (B), as well as in polyunsaturated (C) and monounsaturated (D) membranes in the presence of cholesterol. Data was analyzed after 5 hours of incubation of the SLBs with either HDL (0.132 mg/mL), S protein (0.05 mg/mL) or a mixture of both HDL and S protein (0.132 and 0.05 mg/mL, respectively) in h-TBS at 37 °C.

Figure 2: Graphical representation of how an individual’s lipid composition affects the relationship between HDL and the S protein. Depending on the donor lipid profile, spike protein modifies HDL activity.