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

Stephan Tetter, Naohiro Terasaka, Angela Steinauer, Sam Clark, Andrew J.P. Scott, Nikesh Patel, Marc Leibundgut, Emma Wroblewski, Nenad Ban, Peter G. Stockley, Reidun Twarock, Donald Hilvert*, Richard John Bingham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1220-1224
Number of pages5
Issue number6547
Publication statusPublished - 11 Jun 2021

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