News — A research team led by , Professor of in the College of Arts and Sciences at Indiana University Bloomington, has uncovered new details about how a tiny virus builds its protective outer shell.
The , published in Science Advances by Professor Morais, , also a Professor of Molecular and Cellular Biochemistry in the College, and colleagues from the University of Texas Medical Branch at Galveston and the University of Minnesota, focuses on a virus called phi29 which infects bacteria, and explains how the virus assembles its shell—a crucial part of its ability to infect cells.
This discovery could help fight infections, particularly as certain bacteria become resistant to antibiotics. For example, some bacteria, like Staphylococcus aureus (staph) and Escherichia coli (E. coli) have become harder to treat with traditional antibiotics, creating a growing need for alternative treatments. Phi29 is a type of bacteriophage, a virus that targets bacteria. Thus, researchers are exploring how bacteriophages, including phi29, could be used to target disease-causing bacteria and serve as treatments for antibiotic-resistant infections.
The study’s findings also has implications for nanotechnology—the science and engineering of designing materials and devices that are so small—measured in billionths of a meter—that they can interact with molecules and atoms to create advanced applications in medicine, electronics, and materials science. Therefore, understanding how viruses assemble their protective shells could both lead to new methods of fighting infections and inspire new nanotechnologies.
What is a virus shell, and why is it important?
A virus is akin to a tiny machine with a protective shell called a capsid, which protects the virus’s genetic material. The capsid is made of protein pieces that fit together to form the hard shell.
“Think of the capsid like a delivery box, in that if the box isn’t put together properly, the contents inside—the virus’s genetic material—can’t get to where they need to go, and the virus can’t infect a cell,” explained Professor Morais. “In the case of phi29, the capsid is essential for the virus to carry its DNA to bacteria, where it can take over and replicate. Without a proper shell, the virus can’t survive.”
Morais, who also the faculty co-director of IU’s , and the research team used (cryoTEM)—special microscopes—in order to visualize the steps the virus goes through to build the capsid. CryoTEM is an advanced imaging technique that allows scientists to observe biological samples at very high resolutions, and is particularly useful for studying viruses and other tiny structures like proteins, as it can provide 3D images without damaging a sample.
What the scientists discovered was that the phi29 virus doesn’t just snap together all at once; instead, it goes through stages. First, the virus starts with a “scaffold,” which, as its name suggests, serves a temporary framework to construct the capsid. Then, it adds proteins that will eventually form the hard, final shell. And as the virus builds, the scaffold gets removed, and the capsid takes its final shape.
“We were able to see how the virus puts everything together, step by step,” Morais said. “This is important because it helps us understand how viruses work, and how we can stop them from becoming infectious. It can also teach us how to design and assemble structures on the nano-scale.”
Implications for improved medical treatments
In this light, the new research could help scientists design better treatments for infections. Many viruses, including the flu or common cold, rely on similar processes to build their protective shells. By understanding how these shells are made, scientists could develop drugs that stop the shell from forming, preventing the virus from spreading.
Importantly, this research could help scientists combat human diseases such as the flu, or even viruses that cause diseases like COVID-19. Even though each virus is different, many of them build their shells in similar ways. By knowing exactly how the capsid forms, scientists can figure out ways to stop these viruses before they can make humans sick—a step toward in helping people stay healthier and safer.
In addition, this research could lead to new ways to directly fight bacteria. For example, bacteriophages like phi29 could be used as a type of “virus medicine” to attack harmful bacteria instead of using antibiotics. Thus, understanding how viruses like phi29 build their shells could help lead to breakthroughs in medical treatments.
Driving innovation in nanotechnology
The study also offers new insights into molecular self-assembly, a foundation of nanotechnology. Remarkably, virus capsids self-assemble with high precision; it is as if scattered LEGO pieces spontaneously formed to build a complete structure. Further, understanding how phi29’s structure shifts between assembly and reconfiguration may also inspire the creation of stable, functional, and adaptable nanostructures—smart materials capable of changing shape or function in response to their environment—an area of great interest in biomolecular engineering. Researchers studying phi29’s scaffold proteins are uncovering new ways to embed these self-assembly properties into synthetic nanomaterials, paving the way for more efficient nano-manufacturing.
Thus, by studying how phi29’s scaffold proteins guide its capsid formation, scientists may uncover new strategies for engineering virus-like structures capable of transporting medicine, vaccines, genes, or therapeutics directly to specific cells. For example, these molecule-sized containers could deliver medicine directly to sick cells, like cancer treatments that only target cancer cells without harming the rest of the body or causing side effects.
Such innovations could redefine biomedical engineering, making nano-fabrication more efficient and opening new possibilities in designing advanced materials at the molecular level.
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