Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein

• Published in: Science (American Association for the Advancement of Science) Vol. 372; no. 6547; pp. 1220 - 1224
• Main Authors: Tetter, Stephan, Terasaka, Naohiro, Steinauer, Angela, Bingham, Richard J, Clark, Sam, Scott, Andrew J P, Patel, Nikesh, Leibundgut, Marc, Wroblewski, Emma, Ban, Nenad, Stockley, Peter G, Twarock, Reidun, Hilvert, Donald
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 11.06.2021
• Subjects: Amino Acid Substitution; Amino acids; Aquifex - enzymology; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Capsid - chemistry; Capsid - metabolism; Cellular structure; Cryoelectron Microscopy; Directed evolution; Directed Molecular Evolution; Electron microscopy; Encapsidation; Evolution; Genomes; Interfaces; Intermediates; mRNA; Multienzyme Complexes - chemistry; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Nuclease; Nucleic acids; Nucleocapsid - chemistry; Nucleocapsid - genetics; Nucleocapsid - metabolism; Nucleocapsids; Oligomerization; Packages; Packaging; Protein Domains; Protein Structure, Secondary; Protein Subunits; Proteins; Ribonucleases - metabolism; Ribonucleic acid; RNA; RNA, Messenger - chemistry; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vaccines; Virions; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abg2822

Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.