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

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody 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 CXCL12β, 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.

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

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody 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 CXCL12β, 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.

Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines

Human cytomegalovirus (HCMV) is a common viral pathogen of solid organ transplant recipients, neonates, and HIV-infected individuals. HCMV encodes homologs of several host genes with the potential to influence viral persistence and/or pathogenesis.

Chemokines – role in inflammatory and cancer diseases

Over 50 human chemokines are known at present; the number of the newly discovered compounds from this group still grows. These proteins of low molecular weight, belonging to the family of cytokines with chemotactic properties. Chemokines participate in the physiological and pathological processes of the organism. Recent papers show their role in the processes of embryogenesis, organogenesis, allergies, wound healing, angiogenesis and apoptosis, the course of viral and bacterial infections, autoimmune diseases and cancerogenesis. Chemokines play crucial role in activation and migration of immune cells. Being a key player in chronic inflammation, chemokines may interfere the processes of cellular differentiation and contribute to loss of control over proliferation. Coexistence of inflammatory and cancerogenesis processes, impact of chemokines on cells associated with the tumor and stromal cells, mechanisms of immunological escape is considered to be a current scientific issue. Newly discovered functions of chemokines may reveal their new roles and create the new therapeutic perspectives. It is important to understand the relationship between the structure and function of chemokine receptors, the regulation of their signaling pathways and the genetic and epigenetic mechanisms that regulate the expression of chemokines and their receptors. This article presents the current state of knowledge regarding the construction and classification of chemokines and summarizes the most prominent roles of chemokines. Chemokines are still the subject of many scientific studies, new functions are being discovered. It gives an opportunity to limit the development of many dangerous diseases.