
Brightly rendered and densely carpeted with proteins, the molecule resembles nothing so much as a shaggy beach ball.
It’s actually the Zika virus, as depicted in an article published Tuesday in the journal Structure. And it’s the sharpest image ever created of Zika, or of any other enveloped virus, according to the study’s authors.
Researchers say that the new high-resolution image will lay the groundwork for better diagnosis, treatment, and even a vaccine for the virus, which made headlines in 2015 after it led to a rise in microcephaly among babies of infected mothers in Brazil. As of February 2018, the virus had spread to 86 countries across four continents, according to a report from the World Health Organization.
To get up close and personal with Zika, Michael G. Rossmann and a team at Purdue University used cryo-electron microscopy, an imaging technique that relies on flash-frozen samples to preserve cells that would otherwise be destroyed by the electron beam.
The results were striking. The technique allowed them to see Zika at a resolution of just 3.1 angstroms.
For reference, Rossman said, that’s really, really small. “The distance between atoms is usually on the order of about an angstrom,” Rossman said. “So we have a pretty good idea at three angstroms what the atoms are doing.”
At that resolution, the researchers could make out the side chains of the virus’s proteins, which had been difficult to see in earlier images by other groups. And when they compared the new Zika image with similarly sharp models of related viruses, like Japanese encephalitis and the dengue virus, they noticed important structural differences — especially in the regions of the viruses that they believe are responsible for binding to and infecting cells.
Such differences could help explain why different viruses infect different types of cells, said Madhumati Sevvana, the study’s first author. She added that they could also be used to create more effective diagnostic tools.
“Getting the more accurate structure also informs us what can attenuate the structure and what might make a good vaccine,” Rossmann said. “It gave us a lot of basic information about how we can use the virus to fight disease.”
But the findings are still a long ways away from formulating a functioning Zika vaccine, Sevvana noted.
“From the structures, we can only guess which regions would be responsible for interacting with different kinds of receptors,” she said. “The structures should be followed by biochemical and mutagenic experiments.”
In the findings, Rossmann saw an analogy to something a little bigger than 3 angstroms.
“If you buy a car, you maybe don’t know how it works,” Rossmann said. “If it breaks down, you don’t know what to do about it. But if you study exactly how the engine works, if you become a mechanic, then you have much better control over the car. You know what the machine does and how it works.”
“That’s what we’re doing,” he continued. “We’re learning how these viruses work. Then we can manipulate the virus and avoid disease.”