Advanced proteome and in silico analyses to identify enteroviral disease mechanisms and tissue specific biomarkers

Enteroviruses (EVs) including polio, Coxsackieviruses, and the newly emerging EV68 and EV71, can cause severe illnesses such as poliomyelitis and myocarditis, and have also been linked to type 1 diabetes and cardiomyopathy.

Currently, there are no licensed antivirals for EVs and the only vaccine developed so far for common use is the polio vaccine. EVs encode two proteases (2A and 3C). They are crucial for the virus to propagate and evade the host immune response.

EV-mediated cleavage of host proteins cause pathology, but no studies have attempted to fully reveal the proteins in the human proteome cleaved by the viral proteases (the EV “degradome”).

In this novel and multidisciplinary project, we hypothesize that the cleavage of host proteins is more ubiquitous than previously recognized and that cell type specific degradomes explain different pathological features.

It is our goal to define the viral degradome in disease relevant cell types and use this information to identify mechanisms behind tissue specific pathologies.

This information will also be used for the discovery of organ- or cell specific biomarkers for EV-induced disease in liquid biopsies.

Collectively, our studies will provide unique information on how EVs cause illness and introduce an entirely new concept for disease diagnostics.

The studies will be useful for the development of new antiviral therapies and the approach can be easily implemented for studies on other emerging viruses, including coronaviruses.