Cryo-EM structures and structure-guided design of Atlas virus capsids

Endogenous viruses and retroelements occupy a large fraction of genomes, but the properties of proteins they encode remain largely uncharted. Here, we define Atlas viruses, a new clade of endogenous viruses in nematodes with a retrovirus-like genome organization, phlebovirus-like envelope glycoproteins, and highly divergent Gag proteins. Cryo-EM structures of particles from three Atlas viruses reveal thin-shelled icosahedral assemblies containing 60, 240, 420 or 720 capsid proteins and ranging from 20 to 60 nm in diameter. The capsid fold and assembly interactions are distinct from those of orthoretroviruses but reminiscent of spumaretrovirus and dArc capsids. Atlas capsids package nucleic acids, enter cell by endocytosis, and disassemble at endolysosomal pH. Through structure-guided engineering, we generated recombinant Atlas particles with increased pH resilience and particles displaying a CTLA-4 receptor-targeting tag. This work identifies Atlas capsids as attractive candidates for development as engineerable scaffolds for tissue-specific nucleic acid delivery.