Abstract
The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between the levels of high-density lipoprotein (HDL) particles and the severity of COVID-19, with low HDL levels being associated with an increased risk of severe outcomes. Some studies revealed that HDL binds to SARS-CoV-2 particles via the virus’s spike protein and, under certain conditions, such as low HDL particle concentrations, it facilitates SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) and infection of host cells. Other studies, however, reported that HDL suppressed SARS-CoV-2 infection. In both cases, the ability of HDL to enhance or suppress virus infection appears to be dependent on the expression of the HDL receptor, namely, the Scavenger Receptor Class B type 1 (SR-B1), in the target cells. SR-B1 and HDL represent crucial mediators of cholesterol metabolism. Herein, we review the complex role of HDL and SR-B1 in SARS-CoV-2-induced disease. We also review recent advances in our understanding of HDL structure, properties, and function during SARS-CoV-2 infection and the resulting COVID-19 disease.
Highlights
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the severe respiratory illness called coronavirus disease 2019 (COVID19) [1,2], which is a transmissible respiratory disease affecting 223 countries and, as of August 2021, accountable for more than 200 million confirmed cases and around 4.5 million confirmed deaths worldwide [3]
It was reported that SR-B1mediated redistribution of plasma membrane cholesterol may be independent of its ability to bind high-density lipoprotein (HDL) [74,75]. This suggests a possible mechanism by which SARS-CoV-2 binding to HDL may enhance its infection of cells: due to the virus binding to HDL, the HDL binding to Scavenger Receptor Class B type 1 (SR-B1), and the virus binding to angiotensin-converting enzyme 2 (ACE2), this may bring SR-B1 into proximity to ACE2 on the cellular plasma membrane, resulting in an SR-B1-mediated redistribution of cholesterol in the local environment of ACE2 in such a way as to favor viral entry
Despite the variety of HDL particles, their biosynthesis begins with the synthesis and secretion of the major apolipoprotein (ApoA1) as a lipid-free protein, which acquires phospholipids and cholesterol in the circulation through efflux mediated by ATP-binding cassette transporter (ABC)-A1 to form disc-shaped premature HDL particles [51,102,103,104,105] (Figure 2)
Summary
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the severe respiratory illness called coronavirus disease 2019 (COVID19) [1,2], which is a transmissible respiratory disease affecting 223 countries and, as of August 2021, accountable for more than 200 million confirmed cases and around 4.5 million confirmed deaths worldwide [3]. Others have reported findings with cultured human hepatoma Huh-7 and African green monkey kidney Vero-E6 cell lines, demonstrating that, while low concentrations of HDL promote SARS-CoV-2-mediated infection, higher HDL particle concentrations suppress SARS-CoV-2 infection (compared to the absence of HDL) [27,28] Both the enhancement of SARS-CoV-2 infection by low concentrations and the suppression of SARS-CoV-2 infection by high concentrations of HDL particles appears to be dependent on the expression of the HDL receptor, namely, the scavenger receptor class B type I (SR-B1, encoded by the SCARB1 gene) [29,30], in the target cells [26,28]. To try to shed light on the complex role of HDL in SARS-CoV-2-induced disease, we reviewed recent advances in our understanding of HDL structure, properties, and functions during SARS-CoV-2 infection and the resulting COVID-19 disease
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