LIPID-MEDIATED LOCALIZATION OF POLIOVIRUS RNA-DEPENDENT RNA POLYMERASE

Open Access
Author:
Basu, Rohan
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • David Boehr, Thesis Supervisor
  • Ming Tien, Honors Advisor
  • Craig Eugene Cameron, Thesis Supervisor
  • Scott Brian Selleck, Faculty Reader
Keywords:
  • Viral replication
  • poliovirus
  • replication organelle
  • 3D
  • RNA-dependent RNA polymerase
Abstract:
RNA viruses continue to exert a significant toll on human health globally. Poliovirus is a well-studied RNA virus and serves as an important model system for understanding the life cycles of such viruses. This research was focused on understanding the lipid binding interactions of the poliovirus RNA-dependent RNA polymerase (RdRp) to phosphatidylinositol-4-phosphate (PI4P). PI4P is thought to aid in the localization of poliovirus replication proteins, like RdRp, at host intracellular membranes to form viral “replication organelles.” In order to interrogate the lipid-binding interactions of RdRp, nuclear magnetic resonance (NMR) spectra were collected on samples of poliovirus RdRp variants with and without PI4P to determine if and where any interactions between the lipid and protein occurred. The NMR results were also compared to previous molecular docking studies that suggested potential PI4P binding sites. Based on these NMR spectra, it appears that a docking site near the front side of the RdRp palm domain is favored. More work remains to be done in further interrogating these interactions in environments that more closely resemble biological systems.