P selectin promotes SARS-CoV-2 interactions with platelets and the endothelium

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Host-pathogen interactions are crucial for understanding viral infections.
• The specific host factors influencing SARS-CoV-2 infection remain largely uncharacterized.

Purpose of the Study:

• To identify host genes that confer resistance to SARS-CoV-2 infection using a CRISPR activation screen.
• To elucidate the role of identified genes, particularly P selectin, in SARS-CoV-2 pathogenesis.

Main Methods:

• CRISPR activation screening to identify host genes impacting SARS-CoV-2 resistance.
• Validation of candidate genes using authentic SARS-CoV-2.
• Assessment of P selectin's role in viral binding, infection, and platelet/endothelial interactions.

Main Results:

• 34 novel candidate host genes were identified.
• 7 genes, including P selectin, were validated to suppress SARS-CoV-2 infection.
• P selectin enhances SARS-CoV-2 spike binding to cells and platelets, facilitates viral homing in vivo, and blocking these interactions clears infection.

Conclusions:

• P selectin plays a significant role in SARS-CoV-2 infection by mediating viral interactions with platelets and endothelium.
• P selectin's function extends to other pathogenic coronaviruses.
• Therapeutic strategies involving P selectin modulation, such as mRNA-driven expression, show promise for blocking SARS-CoV-2 infection.