INBRE Seminar Series 

Debra Ponds

Over 3% of the world population is infected with the hepatitis C virus (HCV), a hepatotropic (liver specific) virus that will cause chronic hepatitis in as many as 85% of the individuals infected. In the United States 70% of chronic liver disease is caused by HCV infections, making it the leading indication for liver transplant. At the present time there is no vaccine or cure for HCV.

A major obstacle to the study of HCV is the lack of a system for the culture of live virus. Recently some exciting breakthroughs have been achieved using a hepatoblastoma cell line that will support the replication, release, and infectivity of a specific full-length chimeric genome construct of HCV. However, there are limitations even with this chimeric genome construct as a model in a culture system for HCV.

My research focuses on a culture system for HCV by identifying the morphological differences between primary hepatocytes in vivo where these cells serve as the main substrate for HCV replication, in contrast to in vitro culture where these cells do not support HCV replication. While most research with HCV has utilized cells cultured in a monolayer system, hepatocytes sustained in traditional monolayer cultures quickly lose their differentiated functions and morphology that could impact their permissiveness for HCV. I am exploring the effect of a three dimensional high aspect ratio vessel (HARV) culture system designed by NASA along with an exceptional defined media on the permissiveness of HCV infections in primary human hepatocytes and hepatoblastoma cell lines. My hypothesis is that the more similar in morphology and metabolic processes cultured hepatocytes and hepatoblastoma cells are to in vivo cells, the more susceptible they will be to HCV infections.