Cell & Molecular Biology Program Event
Dr. Joe Klaus
Cellular and Molecular Biology
University of Vermont
Molecular Insight into the Cellular Biology of Arenaviruses
Tuesday October 9th, 2012
Arenaviruses and hantaviruses are enveloped RNA viruses that cause a spectrum of severe and often fatal diseases in humans. There are currently no FDA approved vaccines to prevent infection by either of these groups of viruses, and there is a clear need to generate effective therapeutic options. My dissertation studies have focused on i) using proteomics to define the first comprehensive interactome of a representative arenavirus and hantavirus glycoprotein with human cellular proteins, (ii) interrogating the interactomes for candidate host proteins amenable to antiviral development, and (iii) determining the mechanistic action of these cellular proteins in the viral lifecycle. Data presented will focus on the intracellular cargo receptor ER-Golgi-Intermediate Compartment protein of 53 kDa (ERGIC-53), which has a conserved association with most pathogenic arenavirus and hantavirus glycoproteins. The discovery of multiple pathogen-derived ligands for this otherwise highly selective cargo receptor has generated insight into the cellular biology and biogenesis of arenavirus and hantavirus glycoproteins. Further, the molecular details of the interaction represent a novel mechanism of cargo binding and transport for ERGIC-53 as well as a previously unknown role of this cellular protein outside of its canonical role in the secretory pathway.