Grant: Project Grant

Extracellular or circulating nucleic acids derived from infected or damaged cells can be of virus or self origin. Once recognized and taken up by healthy cells, these nucleic acids rapidly and potently lead to the production of cytokines, including interferon. While interferon is important to protect against infections and cancer, inappropriate interferon responses lead to a variety of diseases, including autoimmunity. While class A scavenger receptors (SRAs) are required for binding and internalization of circulating nucleic acids, little is known about how individual SRA family members carry out these functions. Surprisingly, little is also understood about the cellular trafficking or localization of different nucleic acid species following uptake by SRAs. We have uncovered several unexplained anomalies in how different forms and lengths of nucleic acids traffic within cells and induce interferon following uptake by SRAs. In this grant, we will study the internalization, trafficking and signaling of various forms and lengths of nucleic acids to understand the mechanisms of how they activate cytokines such as interferon. Given that interferon can either prevent disease or cause disease, depending on its regulation, understanding basic mechanisms of interferon production in response to circulating nucleic acids is of critical importance.