Detecting and Imaging Host-Virus Interactions

Abstract

For a eukaryotic virus to successfully infect and propagate in host cells several events must occur: the virion must identify and bind to its cellular receptor, become internalized, uncoat, synthesize viral proteins, replicate its genome, assemble progeny virions, and exit the host cell. While these events are taking place, intrinsic host defenses activate in order to defeat the virus, e.g., activation of the interferon system, induction of apoptosis, and attempted elicitation of immune responses via chemokine and cytokine production. As a first step in developing an imaging methodology to facilitate direct observation of such complex host/virus dynamics, we have designed an immunofluorescence-based system that extends the traditional plaque assay, permitting simultaneous quantification of the rate of viral spread, as indicated by the presence of a labeled viral protein, and cell death in vitro, as indicated by cell loss. We propose that our propagation and cell death profiles serve as phenotypic read-outs, complementing genetic analysis of viral strains. We have adapted our assay for use in a virus detection device that provides identification of known viral strains within a few minutes. In the light of recent events, concern about containing infectious pathogens has taken on a new urgency. In addition to the imaging research, I will spend some time discussing public health issues and what roles people with backgrounds in Electrical Engineering and Computer Science might play in this important field.