Catherine Freije, PhD

Travel Award
$1,500

The Rockefeller University

An alphavirus replicon-based method to study hepatitis B virus core variants and drug resistance in high throughput

Mentor: Charles Rice, PhD

Hepatitis B virus (HBV) remains a global health concern as this virus can establish chronic infection in the liver, and long-term infection can lead to cirrhosis and liver cancer. HBV’s effective vaccine can prevent new infections, but currently approved therapies are not reliably curative for those chronically infected and therefore require lifelong use. Furthermore, HBV is a genetically diverse virus, but methods to study this variation in human liver cells have been limited because virus infection and spread are inefficient. As a postdoctoral scientist, I have been developing new methods to comprehensively study HBV protein variation, specifically focusing on HBV’s core protein, the target of a new class of anti-HBV therapies currently in clinical trials. I have developed an innovative method to initiate HBV genome replication using a single variant per cell. This method has enabled comprehensive studies of core variation to provide new insights into HBV core biology. In addition, I have harnessed this method to profile the potential for drug-resistant variants to emerge following core inhibitor treatment, serving as a valuable technology for prioritizing inhibitors that may be more effective treatments. My efforts have resulted in a flexible tool for studying HBV diversity in cell culture providing new insights into key aspects of HBV variation, replication, and establishment of chronic liver infection.