Journal
SCIENCE ADVANCES
Volume 8, Issue 31, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abp9770
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- Division of Intramural Research of the NIAID
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SARS-CoV-2 nucleocapsid protein induces strong immune responses and manipulates innate immunity.
SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2-infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12., whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV- 1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor-expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.
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