- For the first time, scientists have recorded the formation of individual viruses.
- They used an interferometric microscope to capture the virus assembly process in real-time.
- This could help us better understand how to engineer self-assembling particles and fight viruses.
Biomolecules are too small to observe in detail. Cells usually vary between 1 and 100 micrometers in diameter. Inside a cell, a DNA double helix is about 10 nanometers wide, while the nucleus (cellular organelle) that encloses this DNA is approximately 1,000 times bigger (10 micrometers).
The recent advances in microscopy techniques have enabled researchers to image the structure of viruses with unprecedented resolution, down to the atomic level in each protein. Still, we don’t know how such structures assemble themselves.
Recently, a research team at Harvard University was able to capture images showing the formation of individual viruses. This is the first time someone has obtained a real-time view of the kinetics of virus assembly. The findings could help scientists understand how to fight viruses and engineer self-assembling particles.
What Exactly Did They Observe And How?
Researchers analyzed the most abundant type of virus on Earth, single-stranded RNA viruses. Notable human diseases caused by these viruses include polio, West Nile fever, Ebola virus disease, rabies, common cold, and hepatitis C and E.
They focused on a specific RNA virus that is approximately 30 nanometers wide and has one segment of RNA with 180 identical proteins and 3,600 nucleotides. The proteins form a soccer-ball-shaped structure around the RNA by arranging themselves into pentagons and hexagons. This protein shell of a virus is known as a capsid.
Since the components of RNA viruses are too small and their interactions are too weak, no one had been able to image virus assembly in real-time.
In this study, researchers were able to capture the viruses using interferometric scattering microscopy, an advanced optical technique based on the efficient detection of light scattered by nanoscopic objects. It doesn’t show the structure of the virus but it does uncover the virus’s size and how it changes with time.
Courtesy of researchers
They did this by attaching RNA strands to a substrate and flowing proteins over the surface. They then used the interferometric microscope to record the process – several dark spots appeared and gradually grew darker until they were the size of fully-developed viruses.
By observing the growing spots’ intensities, they determined the number of proteins that were getting attached to each RNA strand over time.
It was a non-reversible process: once the spots started assembling they grew darker and darker until they were done. Some of them took 1 minute to shot up to the intensity of a full virus, while some took more than 5 minutes.
Simulations Versus Reality
Previous computer simulations predicted two kinds of assembly pathways:
- The proteins stick to the RNA in a random manner before rearranging themselves into a capsid.
- A nucleus (a critical mass of proteins) forms before the growth of the capsid.
The research team compared these pathways to actual observations obtained in this study and found that the outcomes matched the second pathway.
They also noticed that all capsids didn’t grow into a full virus. The formation of nuclei must be balanced with the capsid growth. In other words, if a nucleus forms too rapidly, it cannot grow into a full virus.
We still don’t know what makes these proteins come together to form the nucleus. But since we have determined the pathway, we can build new models to study self-assembling nanomaterials.