Presentation by Virally Infected Cells of Antigenic Proteins Utilized in Natural Killer Cell Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) 2256335
TL;DR
The data indicate that antibodies to the S protein alone are unlikely to support ADCC to coronavirally infected cells, and that depletion of anti-S from antisera from infected persons had negligible effect on ADCC.
Abstract
The presence of viral proteins in the plasma membranes of infected cells is essential for natural killer (NK) cell antibody-dependent cell-mediated cytotoxicity (ADCC). However, many enveloped viruses assemble inside cells rather than budding out through plasma membranes. Thus, the presence of viral proteins in plasma membranes of infected cells is uncertain, as is which of several viral structural proteins participates in ADCC. Their presence might represent leftover proteins after virion assembly. To address external viral protein display and its sufficiency for antibody-dependent recognition, we utilized the endemic, cold-causing human coronavirus OC-43, a surrogate virus for SARS-CoV-2. We used NK-92-CD16A lymphocytes as killer cells, OC-43 from BEI, and infected, 51Cr-radiolabeled lung A549 cells as ADCC ‘targets’. Viral proteins were monitored by immunofluorescent microscopy. Antibodies to OC-43 included two monoclonal anti-spike S with human Fc’s, plasma from children who had OC-43 respiratory infections, rabbit affinity purified polyclonal anti-nucleocapsid N and S, and sera from unimmunized rabbits. We found that all the antibody reagents reacted with OC-43 infected cells by immunofluorescent microscopy. Labeling of external viral proteins was punctate. However, only the immune plasma and the non-immunized rabbit sera supported ADCC. The finding with anti-S was surprising since the human mAb 1249A8 anti-S could support Fc-receptor dependent phagocytosis of beads with S protein [PMID35862475]. The finding is consistent with PMID35587364, that SARS CoV-2 S was under-expressed in plasma membranes of infected cells and that depletion of anti-S from antisera from infected persons had negligible effect on ADCC. The finding with anti-N was surprising in light of PMID41060789. Conclusions are premature but the data indicate that antibodies to the S protein alone are unlikely to support ADCC to coronavirally infected cells. University of Nevada, Reno Foundation Award. Viral Immunology (VIR)