Understanding viral evolution

Researchers have recreated a key step in the evolutionary history of viruses in a laboratory experiment

July 7, 2021
The Scitech

Researchers at ETH Zurich have recreated a key step in the evolutionary history of viruses in a laboratory experiment. They succeeded in remodeling a natural protein to create capsids capable of storing genetic material. The study has been published in the journal Science. Researchers at ETH Zurich have managed to recapitulate a potentially pivotal stage in virus evolution in the lab: the creation of a virus-​like protein container capable of storing its own genetic information. In simple terms, viruses are made up of genetic material (RNA or DNA) wrapped in a protein shell. The purpose of the capsid is to protect the genetic material from environmental influences and to aid propagation. Success in storing the genetic material hinges on parts of the capsid being able to accurately recognise the viral genetic material and bind to it according to the lock-​and-key principle.

Researchers led by Donald Hilvert have succeeded in altering a bacterial protein to acquire this capability. They used a protein found in the thermophilic bacterium Aquifex aeolicus. In the bacteria, 60 copies of this protein naturally assemble into tiny, geometrically regular, 12-​sided particles. “These bacterial capsids look a lot like virus shells, except they don’t interact with RNA,” Hilvert explains. To ensure that the capsid proteins do just that, he and his colleagues used genetic engineering to modify the protein so that it can to bind to any RNA molecules they chose. They subsequently carried out an evolution experiment in the laboratory to optimize the system, subjecting it to several rounds of random genetic modification and appropriate selection pressure. The end result was a capsid that specifically enveloped the target RNA molecule. In this way, the scientists succeeded in producing a protein container that efficiently packages its own messenger RNA in its interior. The resulting capsule was larger than the original, containing 240 proteins that self-​assembled into a geometrically regular shell with 42 faces.  Moreover, each particle contained two or three messenger RNA molecules. The researchers, together with colleagues from the Universities of Leeds and York, subsequently showed that the RNA cargo had also changed its three-​dimensional structure in the evolution experiments, enabling a packaging mechanism common to many natural virus families. “In the lab, we were able to show that an RNA molecule and the non-​viral protein it encodes can be altered to produce capsids that efficiently package RNA,” Hilvert says. “This could be similar to the way RNA viruses evolved billions of years ago.”

Source: ETH Zurich news release