Distant viruses share a self-assembly mechanism

Distant viruses share a self-assembly mechanism

The multiple protein subunits (green, purple and red) of the plant-infecting bromo mosaic virus (left) have separate nucleation and growth phases similar to the MS2 bacteria-infecting virus (right). Credit: Brome mosaic virus capsid: Lucas, RW, Larson, SB, McPherson, A., (2002) J Mol Biol 317: 95-108 – rcsb.org/structure/1JS9; 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 – rcsb.org/structure/5MSF

How do the hundreds of individual pieces that make up viruses come together in forms capable of spreading disease from cell to cell?

Solving the mystery of self-assembly could pave the way for technical advances such as molecules or robots that assemble themselves. It could also contribute to more efficient packaging, automated delivery and targeted drug design in our fight against viruses that cause colds, diarrhea, liver cancer and polio.

“If we understand the physical rules of how viruses assemble, we can try to make them form inappropriate structures to hinder their spread,” said Rees Garmann, a chemist at San Diego State University and lead author of a new paper that explored a piece. of the puzzle.

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

In both and possibly other viruses, the protein components form a perfect pattern into pentagons and hexagons forming a symmetrical icosahedral shell, one of the most common shapes among all viruses, thanks to a scaffold provided by a looped and folded strand of RNA.

This video, recorded with the iSCAT microscope, shows individual BMV viruses accumulating at 55x normal rate. Each dark spot is a different virus particle and the darkness of the spot indicates its size. Different particles appear at different times, providing evidence that the viruses assemble in two phases: nucleation and growth. Credit: SDSU

Just as a snowflake needs a few molecules of icy water to surround a dust particle before it crystallizes, a virus’ jungle-gym-like sphere of proteins quickly fuses after a few proteins attach loosely to the RNA.

“Without the interactions between the proteins and the RNA that my students, Fernando Vasquez and Daniel Villareal, were studying, it would take a very long time — weeks, months, maybe never — for this virus to accumulate,” Garmann said.

Still, the entire assembly process, which Garmann and his collaborators captured in detailed videos using an innovative iSCAT (interferometric scattering) microscope, which records individual viruses, takes just minutes.

“The iSCAT technique opened a new window into virus self-assembly,” said Vinothan N. Manoharan, a co-author of the study and the Wagner Family Professor of Chemical Engineering and Professor of Physics at the John A. Paulson School of Engineering. from Harvard and Applied Sciences. “Only by seeing how individual viruses form were we able to determine that they don’t all come together at the same time. That was key to understanding the self-assembly mechanism that the two types of viruses share.”

Garmann says their experiments point the way to the next great mystery of how viruses ensure accuracy and functionality at every step along the assembly line.

Knowing more about how viruses assemble is related to the 1950s physics paradox of how proteins fold into their proper shapes much faster than if they were relying solely on chance encounters — a process estimated to take longer than the billions. years the universe has existed.

One case closed, another open

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

“The hope of our research is to learn more about a physical, fundamental interaction that takes place in these model systems,” said Vasquez, a doctoral student in chemistry. “Maybe with more data and time, they can be applied to study a new virus.”

“Self-assembly — designing components that know how to come together — is completely different from how we build ordinary things,” Garmann said. “As engineers, we can learn a lot from viruses.”

First Virus Compiling Video Released

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

Provided by San Diego State University

Quote: Distantly related viruses share self-assembly mechanism (2022, September 22) retrieved September 22, 2022 from https://phys.org/news/2022-09-distantly-viruses-self-assembly-mechanism.html

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