Integrative structural biology as a toolbox to dissect viral entry

Picornaviruses are a major cause of infections in humans and animals and impact on human health, agriculture and economics.

As all viruses are obligate intracellular parasites, they are totally reliant on the cellular machinery of infected hosts (i.e. host factors) to fulfil the essential steps of their viral life cycle. Identifying and characterizing such host factors yields candidates for the development of novel antiviral therapeutics.

We have recently identified PLA2G16 as an essential host factor for several enteroviruses.

It acts during the final stages of viral entry, by facilitating the genome transfer to the cytoplasm ahead of a viral pore-formation triggered clearance pathway involving the autophagy machinery.Remarkably, some picornaviruses carry a homolog in their genome, which potentially could allow them to bypass the PLA2G16 dependent step and thus render them independent of the host factor.

A dual approach combining structure-function characterization of these proteins in vitro with tracking their spatiotemporal regulation and activity as cells get infected will help us uncover the molecular mechanisms governing their function in the viral life cycle.

This knowledge will help answer still open questions on the picornavirus life cycle, including the evolution of viral proteins, and contribute to the development of novel treatment strategies for these biomedically important viruses.