Bill Jackson
Postdoctoral Fellow

Address:
D311A Fairchild
299 Campus Drive
Stanford CA 94305-5124
 
Telephone:
+1.650.498.7089
 
E-mail:
 
Research Summary

My work has demonstrated that members of the picornavirus family subvert the cellular autophagic machinery during infection. In particular, poliovirus and rhinovirus, a major causative agent of the common cold, induce many of the hallmarks of autophagy during infection. The autophagy pathway plays a variety of roles in cell survival, cell death, protein degradation, and innate immunity. Increasing cellular autophagy increases viral growth, while decreasing cellular autophagy has a negative effect. Viral subversion of components of this pathway serves to generate membranous surfaces, which serve as scaffolds for the viral replication machinery. We have also suggested that the autophagy-like double membrane structures formed during infection facilitate escape of newly formed viruses from the cell prior to lysis.

In my current work I am utilizing a transiently expressed marker for autophagosomes, GFP-LC3 (hAtg8p), to monitor live, real-time movement of vesicles within the cell during infection and in relation to cellular markers and structures. In addition, I am using existing and newly generated mutants of poliovirus and rhinovirus to analyze pre-lytic escape from the cell. These assays are being performed in the presence and absence of reagents which alter the autophagic pathway. The ultimate goal of this work is to shed light on the relationship between viral replication, intracellular membranes, autophagy, and non-lytic viral exit from the cell. This will lead to identification of potential therapeutic targets in viral and cellular proteins related to the autophagy pathway, as well as an understanding of mechanisms involved in persistent viral infections in which cell lysis is limited or undetectable.

Copyright 2006 - 2007. The Laboratory of Karla Kirkegaard, Ph.D. All rights reserved.