After discovering the structure of the viral coat, Rice University scientists are confident of finding novel ways to fight viral infections.
After three years of work, the researchers have created an image of the structure, showing five million atoms-each in precisely the right place.
The image reveals the structure of a type of protein coat shared by hundreds of known viruses containing double-stranded RNA genomes.
Using hundreds of high-energy X-ray diffraction images and paints, the researcher have created the clearest picture yet of the viruses' genome-encasing shell called a "capsid".
"When these viruses invade cells, the capsids get taken inside and never completely break apart," said lead researcher Jane Tao, assistant professor of biochemistry and cell biology at Rice.
Capsids play a major role as viruses can reproduce themselves only by invading a host cell and highjacking its biochemical machinery. But when they invade, viruses need to seal off their genetic payload to prevent it from being destroyed by the cell's protective mechanisms.
Most of the viruses use either a helical or a spherical capsid. The researchers focussed on the spherical variety, and firstly created a crystalline form of the capsid that could be X-rayed.
They chose the oft-studied Penicillium stoloniferum virus F, or PsV-F, a virus that infects the fungus that makes penicillin, and uses the spherical capsid. Although it does not infect humans, it is similar to a rotavirus and others that do.
"Spherical viruses like this have symmetry like a soccer ball or geodesic dome. The whole capsid contains exactly 120 copies of a single protein," said Junhua Pan, a postdoctoral fellow at Rice.
It was shown earlier that spherical capsids contain dozens of copies of the capsid protein, or CP, in an interlocking arrangement.
In the new study, researchers identified the sphere's basic building block, a four-piece arrangement of CP molecules called a tetramer, which could also be building blocks for other viruses' protein coats.
And now that the researchers have deciphered both the arrangement and the basic building block, they are hoping to learn more about the capsid-forming process.
"Because many viruses use this type of capsid, understanding how it forms could lead to new approaches for antiviral therapies. It could also aid researchers who are trying to create designer viruses and other tools that can deliver therapeutic genes into cells," said Tao.
The research team used X-ray crystallography to decipher the structure of the capsid.
After spending months creating hundreds of crystal samples of PsV-F, Pan collected hundreds of high-intensity, high-energy X-ray diffraction images at the Cornell High Energy Synchotron Source, or CHESS, in Ithaca, N.Y.
They, then analysed the way the X-rays scattered when they struck the crystals, and created a precise three-dimensional image of the spherical capsid.
The image appears in the Proceedings of the National Academy of Sciences.