Remotely related viruses share a self-assembly mechanism

The multiple protein subunits (green, purple, and red) of the plant-infecting bromine mosaic virus (left) have discrete nucleation and growth stages similar to the bacterium MS2 virus (right). Credit: Brome mosaic capsid: Lucas, RW, Larson, S. B., McPherson, A., (2002) J Mol Biol 317: 95-108 –; MS2 virus capsid: Rowsell, S., Stonehouse, NJ, Convery, MA, Adams, CJ, Ellington, AD, Hirao, I., Peabody, DS, Stockley, PG, Phillips, SE, (1998) Nat Struct Biol 5: 970-975 –

How do the hundreds of individual pieces that make up viruses assemble into shapes capable of spreading disease from cell to cell?

Solving the self-assembly puzzle could pave the way for engineering advances such as molecules or robots that assemble themselves together. It can also contribute to more efficient packaging, automated delivery and targeted design of drugs in our fight Viruses that cause colds and diarrhea, Liver Cancer and polio.

Reese Jarman, a chemist at San Diego State University and lead author of a new research paper that fills in a piece of the puzzle, said.

Garman, along with two SDSU graduate students and collaborators at Harvard and UCLA, concluded that two distantly related RNA viruses—one infecting bacteria and one infecting plants—perform this chemical dance in strikingly similar ways. .

In both viruses, and possibly other viruses, the protein components Perfectly patterned in pentagons and hexagons forms a symmetrical icosahedral shell, one of the most prevalent among all viruses, thanks to the scaffold provided by a pleated and coiled strand of RNA.

This video, recorded with an iSCAT microscope, shows individual BMV viruses clustering at normal 55x speed. Each dark spot is a different viral particle and the darkness of the spot indicates its size. Different particles appear at different times, which indicates that viruses assemble in two stages – nucleation and growth. Credit: SDSU

Similar to the way a snowflake requires a few particles of freezing water to surround a dust particle before crystallizing, virusThe bush-like ball of protein fuses quickly only after a few proteins adhere loosely to the RNA.

“Without the protein-RNA interactions that my students, Fernando Vazquez and Daniel Villareal, have been studying, it would take a very, very long time — weeks, months, maybe never — for this virus to assemble,” Garman said.

However, the entire assembly process, which Garmann and his co-workers filmed in detailed videos using an innovative iSCAT (interferometric dispersal) microscope that records individual viruses, takes just minutes.

“iSCAT technology has opened a new window on virus self-assembly,” said study co-author Venuthan Manoharan and professor of chemical engineering and professor of physics at Harvard University’s John A. Paulson School of Engineering. applied Sciences. “Only by seeing individual viruses form, we can determine that they do not all assemble at the same time. This was the key to understanding Self-assembly A mechanism shared by both types of viruses.

Garmann says their experiments point the way to solving the next big puzzle of how viruses ensure accuracy and functionality at all steps along assembly line.

Learning more about how viruses assemble relates to the physics paradox of the 1950s about how proteins can form into their proper shapes much faster than if they relied solely on chance encounters — a process estimated to take longer than billions of years in the universe.

One case closed, others opened

Although the viruses in this study and the virus that causes COVID-19 both contain RNA, the researchers say it would be premature to extend these findings to the larger, more exotic SARS-CoV-2 virus.

“The hope of our research is to learn about some of the basic physical interactions that occur in these model systems,” said Vasquez, a doctoral student in chemistry. “Maybe with more data and time, it could be applied to studying a new virus.”

“Self-assembly — designing components that know how to assemble — is very different from how ordinary things are built,” Garman said. “As engineers, we have a lot to learn from viruses.”

Release of the first virus collection video

more information:
Rees F. Garmann et al., Single-particle studies of the effects of RNA-protein interactions on the self-assembly of RNA virus particles, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2206292119

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