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

Area of Science:

• Biochemistry
• Virology
• Lipid Metabolism

Background:

• A strong association exists between SARS-CoV-2 and lipoproteins, particularly HDL.
• COVID-19 severity correlates inversely with plasma HDL levels.
• The SARS-CoV-2 spike (S) protein is known to bind HDL, potentially depleting lipids and altering function.

Purpose of the Study:

• To confirm the interaction between the SARS-CoV-2 S protein and HDL.
• To investigate the S protein's lipid preferences and its impact on HDL function.
• To explore how individual lipid profiles influence the S protein's effect on HDL.

Main Methods:

• Neutron reflectometry (NR) was employed to study HDL-S protein interactions.
• HDL's ability to efflux cholesterol from macrophages was assessed.
• Lipid profiles of individuals (triglycerides and cholesterol levels) were analyzed in relation to S protein effects.

Main Results:

• Observations confirmed that the SARS-CoV-2 S protein binds to HDL, affecting its lipid content and function.
• The S protein demonstrated a preference for specific lipids within the HDL particle.
• The impact of the S protein on HDL function varied significantly across different lipid profiles (LTHC, HTHC, LTLC).

Conclusions:

• The SARS-CoV-2 S protein interacts with HDL particles.
• This interaction impairs HDL function, with effects modulated by the individual's lipid serum profile.
• The S protein's interaction with HDL contributes to lipid metabolism imbalance during COVID-19 infection.