Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• The SARS-CoV-2 nucleocapsid protein (N) is known to elicit strong immune responses.
• While typically localized intracellularly, N protein is detectable on the surface of live infected or transfected cells.

Purpose of the Study:

• To investigate the extracellular functions and immune implications of SARS-CoV-2 N protein.
• To explore the potential of N protein as a target for broad-spectrum coronavirus vaccines.

Main Methods:

• Detection of N protein on the surface of live cells.
• Assessing N protein binding to cell surfaces and its interaction with glycosaminoglycans and chemokines.
• Evaluating the effect of anti-N antibodies on N-expressing cells and Fc receptor-bearing cells.
• Analyzing N protein's role in chemokine sequestration and leukocyte chemotaxis.

Main Results:

• Cell surface N protein binds to heparan sulfate and heparin on neighboring cells via high-affinity electrostatic interactions.
• N protein binds to and inhibits the chemotaxis of human chemokines, such as CXCL12β.
• Antibodies against N protein bound to cell surface N can activate Fc receptor-expressing cells.
• N protein's conserved antigenicity across human coronaviruses was confirmed.

Conclusions:

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