Deciphering mechanism of Enterovirus-D68 (EV-D68) neuropathogenesis via whole genome yeast two hybrid interactomics.

To date, there are no genome-wide studies that directly identify human genes required for EV D68 viral infection, which will be of great interest and utility for the broader scientific community. Discovery of host genes and pathways that mediate pathogenesis of Enterovirus D-68 (EV D-68) is a critical resource that may promote our understanding of how these viruses cause disease, why there is variable host susceptibility, and the origins of host species range and may reveal host-directed therapeutic targets against known and unknown enteroviruses. We believe that there is great potential in systematically exploring the host dependencies of the EV D-68 virus to identify other host proteins that are already targeted by existing drugs. Therapies that target the host–virus interface, where the emergence of mutational resistance is arguably less likely, could potentially present durable, broad-spectrum treatment modalities. Unfortunately, limited knowledge of the molecular details of EV D-68 precludes a comprehensive evaluation of small molecule candidates for host-directed therapies. We sought to address this gap by systematically mapping the interaction landscape between EV D-68 and host via yeast two hybrid (Y2H) whole genome screening.