Functional Interrogation of the Host Proteome during Viral Infection

Viruses are a diverse family of pathogens known to infect all life forms on the planet. RNA viruses in particular have been the causative agents of several pandemics in recent history including the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the 2009 swine flu pandemic caused by the H1N1 influenza A virus, and many other public health emergencies such as the Ebola and Zika virus epidemics. Enteroviruses, a subgroup of the picornavirus family are a diverse class of RNA viruses (most notably poliovirus), that cause several diseases, ranging from encephalitis and paralysis to respiratory diseases. Several large outbreaks of non-polio enteroviruses in North America and Europe have caused great concern about future pandemics. To better understand the host response to these viruses, we analyzed the reprogramming of the cellular proteome in response to enterovirus D68 (EV-D68) infection, a clinically-relevant enterovirus with pandemic potential. To do so, we employed mass spectrometry (MS)-based proteomics, a powerful technology that allows for the quantitative analysis of protein level changes and identified novel proteins with significant expression level changes. Our current proposal will aim to characterize the role of these novel targets and investigate their mode of regulation during infection. We aim to uncover promising new targets which could form the basis of new antiviral therapeutics and increase our fundamental knowledge of host immunity.