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 protein is typically localized within the cell's cytosol.

Approach:

• Investigated the surface localization of SARS-CoV-2 N protein on live cells.
• Examined the binding interactions of N protein with cell surfaces and chemokines.
• Assessed the impact of N protein on leukocyte chemotaxis and innate immune cell activation.

Key Points:

• SARS-CoV-2 N protein is detectable on the surface of infected and transfected cells.
• N protein binds to heparin and heparan sulfate on cell surfaces and sequesters chemokines like CXCL12β.
• Antibodies targeting cell surface N protein activate Fc receptor-expressing immune cells.

Conclusions:

• Cell surface N protein modulates 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 vaccines inducing broad cross-reactive immunity.