Cell Surface SARS-CoV-2 Nucleocapsid Protein Modulates Innate and Adaptive Immunity

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• The SARS-CoV-2 nucleocapsid protein (N) is known to elicit strong immune responses.
• N is typically considered a cytosolic protein, but its presence on the cell surface is increasingly recognized.

Approach:

• Investigated the localization and function of SARS-CoV-2 N protein on the surface of infected and transfected cells.
• Examined the binding interactions of N protein with cell surface molecules and chemokines.
• Assessed the immunomodulatory effects of cell surface N protein and its potential as a vaccine target.

Key Points:

• SARS-CoV-2 N protein is detectable on the surface of live cells and binds to heparin and heparan sulfate.
• Cell surface N protein binds to and inhibits the function of human chemokines, including CXCL12β, affecting leukocyte chemotaxis.
• Antibodies against N protein on cell surfaces can activate Fc receptor-expressing immune cells.

Conclusions:

• Cell surface N protein plays a role in innate immunity by sequestering chemokines and can be targeted by immune cells.
• The conserved antigenicity of N protein across human coronaviruses makes it a promising candidate for developing vaccines that provide cross-reactive immunity against SARS-CoV-2 variants and other coronaviruses.