BPS2026 – Identifying the TAM receptor tyrosine kinase involved in non-enveloped virus infection

Viral infection is initiated through attachment of the virus particle to the host cell surface. This involves surface viral proteins binding to cell receptors, priming the virus for entry through mechanisms such as endocytosis or viral-cell membrane fusion. RNA viruses like poliovirus mediate attachment to the cell through hydrophobic interactions between the canyon-shaped outer surface of the virus and CD155 expressed on the cell surface. Poliovirus then undergoes structural changes that allow it to enter the cell through endocytosis. While CD155 has been established as the sole receptor for poliovirus infection, it has been recently demonstrated that TAM receptor tyrosine kinases may also be involved. TAM receptor tyrosine kinases, consisting of Tyro3, Axl, and Mer, are single-pass transmembrane receptors that mediate various cellular and metabolic signaling pathways. When bound and activated by ligands such as Gas6 or protein S, these receptors can induce phagocytic clearance of apoptotic cells and attenuate innate immune inflammatory responses. Our preliminary data show that pan-TAM receptor inhibition causes a dose-dependent decrease in poliovirus spread to uninfected cells in culture. The goal is to identify which TAM receptor works with CD155 to initiate poliovirus infection through drug inhibition and receptor knockout studies. Additionally, we want to determine to what extent does the identified TAM receptor dictates whether poliovirus undergoes a lytic versus non-lytic infection program in vitro. The results from this research will provide novel insights into non-canonical TAM receptor function in viral infection, which can lead to the development of targeted therapies against similar RNA viruses.