Development of Cell Culture Based Methodology to Study Hepatitis C Virus (HCV) Replication
Guest Speaker: Dr Mohsan Saeed (PhD)
Research Associate, Rockefeller University, USA
Date: July 26, 2017 (Wednesday)
Time: 3 pm – 4 pm
Venue: Smart Room, SBASSE 4th Floor
Host: Dr. Syed Shahzad-ul-Hussan
Abstract:
According to estimates, approximately 160 million people worldwide are currently infected with the Hepatitis C Virus (HCV). Despite recent incredible advances in anti-HCV therapy, several aspects of the virus lifecycle remain unknown. This is mainly because of the frustratingly slow progress in the development of HCV cell culture systems. For years, HCV subgenomic replicons were used to study the virus RNA replication in human hepatoma cells. However, these replicons replicate only after they accumulate cell culture-adaptive mutations, and it was unclear why wild-type HCV fails to replicate in cell culture. We hypothesized that the human hepatoma cells might lack critical factors required for the replication of wild-type HCV. To test this idea, we performed a large-scale overexpression screen and identified a protein, SEC14L2, which facilitates replication of wild-type HCV in cultured cells. Most remarkably, expression of this protein allowed for growth of HCV clinical isolates in cell culture for the first time. This discovery will help provide deeper insights into molecular details of the HCV lifecycle and allow testing of new HCV drugs. I will present our work on the discovery of SEC14L2 as a critical HCV replication factor.
Biography:
Dr. Saeed is currently working as a Research Associate at The Rockefeller University. He received his PhD from the University of Tokyo, Japan working on various aspects of the HCV life cycle. The highlights of his graduate work include characterisation of HCV variants recovered from the experimentally infected chimpanzees, study of the role of the endoplasmic reticulum in the HCV life cycle, and development of the first subgenomic replicon system for HCV genotype 3a. For his postdoctoral training, he joined the Centre for The Study of Hepatitis C at The Rockefeller University, and continued working on HCV. His most valuable contribution during this time was the development of a cell culture system that allowed, for the first time, HCV clinical isolates to grow in the laboratory. This work, published in Nature in 2015, provides an excellent platform to quickly advance HCV research and develop novel antiviral strategies. In recognition of his outstanding work, The Rockefeller University nominated him for the Blavatnik Award 2016.