Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs

Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs

Blog Article

Abstract Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions.Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention.Here, we describe the pan-viral Mid Rise Relaxed Short discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses.We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry.Using structural and biophysical analyses, we show that viral mimicry-based Glass Plate interactions have similar binding strength and bound conformations as endogenous interactions.

Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development.Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.