Dissecting the peptide motifs controlling coronavirus infections

PROJECT SUMMARY/ABSTRACT This proposal aims to evaluate coronavirus assembly and egress. These late infection stages are understudied relative to coronavirus entry replication. Additional research is necessary to reveal how host cell machineries facilitate assembly and egress. Therefore, this proposal specifically focuses on coronavirus membrane proteins, their interactions with host cell components, and the relevance of these contacts to efficient virion formation and emergence from infected cells. Guided by biochemical and protein structural data documenting interfaces between viral peptide motifs and host coatomer and retromer complexes, we will construct recombinant murine coronaviruses and corona virus‐like particles with alternative motifs. Comparisons of recombinant virus infections, along with reductionist approaches assessing the formation and subcellular transport of virus‐like particles, will reveal how coatomer and retromer‐sorting nexins operate in controlling viral membrane protein trafficking, virus particle formation, and particle egress pathways. By expanding the studies to human pathogenic coronaviruses, we expect to identify commonly utilized host machineries that might be targeted by antiviral therapeutics.