Profiles

The host innate immune response is the first line of defense against viral infections. Cytosolic sensors in the host cell recognize the incoming virus and stimulate the production of types I and III interferons (IFNs) with direct antiviral activities. The same or neighboring cell binds secreted IFNs and triggers the JAK/STAT signaling pathway resulting in the expression of a wide array of IFN-stimulated genes (ISGs). Many of these ISGs target different steps of the viral life cycle, but only some of them have been characterized. A main focus of the Li Lab is to elucidate the mechanisms of antiviral IFNs and ISGs using molecular biology, biochemistry, genome-wide approaches, and stem cell culture systems. We are studying the host and viral determinants that modulate viral infections in the presence of antiviral ISGs in different cell contexts using arthropod-borne alphaviruses as our model system. Several projects in the lab focus on the mechanism of zinc finger antiviral protein (ZAP), a broad-spectrum antiviral ISG that inhibits a broad range of viruses, and how it synergizes with its co-factor, the host E3 ubiquitin ligase TRIM25. Understanding the antiviral mechanisms of ISGs not only will shed light on how the host distinguishes between self and non-self, but it will also uncover viral antagonism strategies of the host innate immune response that drive increased viral virulence and pathogenesis.