Researchers see individual virus formation for the first time

In a first, researchers have captured images of the formation of individual viruses, providing a detailed view of the mechanism with which particles self-assemble into the parasite -- an advance that may help us find new treatment approaches for viral diseases.

The study, published in the journal PNAS, looked at the formation of single-stranded RNA viruses -- the most abundant type of virus on the planet that is responsible for diseases like the West Nile fever, gastroenteritis, hand, foot, and mouth disease, polio, and the common cold.

The researchers, including those from Harvard University in the US, studied an RNA virus that infected the bacterium E. coli.

The virus was about 30 nanometres in diameter (thousands of times smaller than the width of a single human hair), and had one piece of RNA with about 180 identical proteins, the study noted.

According to the researchers, the proteins arranged themselves into hexagons and pentagons to form a soccer-ball-like enveloping structure around the RNA, called a capsid.

The researchers mentioned that until now, scientists had not been able to observe how proteins formed the capsid structure in real time since the parasites and their components were very small, and their interactions were very weak.

To unravel this mystery, the researchers used a viewing technique known as interferometric scattering microscopy, in which the light scattered by an object created a dark spot in a larger field of light.

The technique, the study noted, does not show the virus' structure, but reveals its size and how that changed with time.

When the researchers, attached viral RNA strands to a medium, and flowed proteins over the surface, they could see dark spots appear and grow steadily until they were the size of full-grown viruses.

As the researchers recorded the intensities of the growing spots, they could determine how many proteins were attaching to each RNA strand over time.

"One thing we noticed immediately is that the intensity of all the spots started low and then shot up to the intensity of a full virus," said Vinothan Manoharan, co-author of the study from Harvard University.

Manoharan added that the shooting up happened at different times with some capsids assembled in under a minute, some taking two, three, or even more than five minutes.

"But once they started assembling, they didn't backtrack. They grew and grew and then they were done," he said.

When the researchers compared their results to previous computer simulation experiments, they could conclude that the main pathway leading to the formation of an individual virus required a critical mass of proteins, called a nucleus, to form before the capsid could grow.

The study noted that the nucleus formed at different times for different viruses, but once it did, the virus grew rapidly, without halting, till it reached the right size.

The viruses also tended to assemble wrongly more often when more proteins were flowing over the substrate, the researchers said.

The researchers said that viruses assembling in this manner may have to balance the formation of their nuclei with the growth of the capsid.

They added that the complete capsids may not grow if the nuclei formed too quickly.

"That observation might give us some insights into how to derail the assembly of pathogenic viruses," said Manoharan.

The researchers still haven't cracked the puzzle of how the nucleus assembled but with the current study identifying the virus formation mechanism, they plan to develop new models to understand nucleus assembly within that pathway.

The researchers added that their models might also be useful for designing nanomaterials that assemble themselves.