ISG15 at the interface of innate immune response and metabolic pathways during respiratory viral infections

In spite of significant advances in virology, emerging and re-emerging respiratory viral infections caused by human pathogenic coronaviruses and Influenza virus remain a major threat to human health. At present there is no specific antiviral agents or vaccine against most of these viruses. While each of these viruses are structurally different they often share similar host innate response.

In severe form, these viruses cause acute respiratory distress that is characterized by a dysregulated immune response and metabolic alterations and the link between these two biological processes are still not well characterized.

Interferon stimulatory gene 15 (ISG15) can bind to several proteins of interferon (IFN) signaling and metabolic pathways and alter their functions.

Using advanced multi-omics and cell culture systems will test the hypothesis that ISG15 induced during viral infections integrates a diverse array of signals that control innate immune response and cell metabolism.

To test this, we will i) identify and integrate the immunological and metabolic changes during virus infection, ii) investigate the role of ISGylation in regulation of these pathways and finally iii) create ex vivo and in vivo models to explore the regulatory mechanisms in a more physiological condition.

The study will provide new possibilities for therapeutic modulation of immune-metabolic responses against RNA viruses that are responsible for most of the fatal epidemics and pandemics.