Shining a Light on Picornavirus Entry

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

As obligate intracellular parasites, viruses must depend 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 previously identified PLAAT3 as an essential host factor for several enteroviruses.

It acts during the final stages of viral entry, by facilitating genome transfer to the cytoplasm ahead of a viral pore-formation triggered clearance pathway involving the autophagy machinery.Remarkably, some picornaviruses carry a homolog called 2A protein in their genome that could potentially allow them to bypass the PLAAT3-dependent step and thus render them independent of the host factor.

Tracking their spatiotemporal regulation and activity as cells get infected and characterizing their mode of genome transfer in vitro 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 to target viral entry for these biomedically important viruses. Any new host-factors identified and characterized in this study could reveal new therapeutic targets.