PROJECT SUMMARY Mechanisms of acute and long-term antiviral antibody responses Two biophysical attributes shared by most animal viruses are the display of viral-specific proteins at certain densities on the surface of individual virions and the encapsulation of viral genome inside the virion. A threshold density of viral surface proteins is important to ensure efficient viral infection of host cells. From the perspective of the host, a threshold density of viral surface proteins may also be critical for the recognition by germline B cells for efficient mounting of humoral responses. The encapsulated genetic material can also stimulate B cells through the Toll-like receptors. Substantial mechanistic studies at the single-molecule level and imaging of live cells have revealed the sensitivity of B cells to the density of antigens. However, at the mechanistic level, it remains largely uncharacterized how B cells may recognize and respond to the individual as well as collective attributes of a virus, including the spatial density of proteins and the internal nucleic acids. To this end, we have developed a new system of synthetic virus-like structures (SVLS), and we are using these structures as a new generation of virus-like immunogens to study both in vitro and in vivo fundamental mechanisms of B cell antiviral responses. This project aims to unravel the acute and long-term antiviral antibody responses using this new generation of model particulate antigens that we have developed and train the next generation biomedical and pharmaceutical sciences workforce. The success of this project will yield new and important mechanistic information on the initiation and maintenance of neutralizing antiviral antibody responses in mice, and prepare the trainee for his long-term scientific and professional career.