The viral reproductive cycle requires self-assembly, maturation of viral particles and, after infection, the release of genetic material into the host cell. New technologies in machines allow scientists to study the dynamics of this cycle and eventually find new treatments. As a physical virologist, Wouter Roos, a physicist at the University of Groningen, together with two long-time colleagues, wrote a review paper on these new technologies, published in the journal Nature Reviews Physics January 12.

“Physics has been used for a long time to study viruses,” Roos said. ‘The laws of physics govern important events in their reproductive cycles.’ Recent advances in physics-based techniques have made it possible to study self-assembly and other steps in the reproductive cycle of single virus particles and at second resolution. “These new technologies allow us to see the dynamics of the virus,” added Roos.

Energy

In 2010, he published for the first time a review paper on the physical aspects of virology with two of his colleagues. ‘Back then, almost all virus research was relatively static, for example putting pressure on a virus particle to see how it reacted.’ At that time, studies of dynamic processes, such as self-assembly, were performed in bulk, without the option of magnifying individual particles. ‘This has changed over the last few years and so we thought it was time to reconsider.’ This paper, ‘The Physics of Virus Dynamics’, was co-authored by Robijn Bruinsma from the University of California at Los Angeles (USA) and Gijs Wuite from VU Amsterdam (Netherlands).

Viruses attack cells and force them to make proteins for new viral particles and copy their genetic material (RNA or DNA). This results in a cytoplasm filled with parts of the virus that self-assemble to produce enveloped RNA or DNA elements. ‘No external energy is required for this process. And even in a test tube, most viruses will synthesize themselves quickly. ‘ This process is normally studied in large numbers, averaging the behavior of a large number of viral particles. ‘So we don’t know about the variance in the set of individual particles.’

Sub-second scans

Over the past few years, technologies have been developed to study these individual particles in real time. One of them is the high-speed atomic force microscope (AFM). Atomic force microscopy scans surfaces with an atom-sized tip and can thus map their topology. Roos, who uses high-speed AFM, said: ‘Recently, the scanning speed of AFM has increased significantly and now we can perform sub-second scans of surfaces less than 1 square micrometer in size using High speed AFM. This allowed us to see how the viral subunits assemble on the surface. It’s a very dynamic process, with blocks being built and released.

‘ Single-molecule fluorescence is also used to study viruses, for example, the attachment of viral proteins to DNA. ‘Using optical tweezers, we hold two small beads at the ends of the DNA molecule. When the viral proteins bind to the DNA, it coils up and brings the two particles closer together. This is visualized by fluorescent markers attached to the beads. ‘ In addition, fluorescently labeled proteins can be observed while they are attached to viral DNA or to other proteins. The third technology is to use optical microscopy to measure the interference of light scattered by virus particles. These patterns reveal the structure of the particles during assembly.

The process of increasing durability

Other steps in the viral cycle can also be studied. “After they self-assemble, the particles need to be more resilient to withstand conditions outside the host cell,” says Roos. Other transformations also occur, preparing the particles to infect other cells. The dynamics of this maturation process are important to our understanding of how viruses work. ‘And after infecting the new cells, the virus particle must detach to release its genetic material.’

New technology is now revealing the physical dynamics of the virus. It allows scientists like Roos and his colleagues to study how genetic material is combined and what physical principles drive this process. Most antiviral drugs interrupt the first steps of infection, such as the binding of viral particles to their host cells. Using this new information, we can develop drugs that block self-assembly or other key steps in the virus’s reproductive cycle.

Nanotechnology

A deep understanding of the physics of viral particles is also important to use them in research, for example as building blocks in nanotechnology or as antigen carriers in vaccines. Some of the leading COVID-19 vaccines use adenoviruses to deliver the gene for the SARS-CoV-2 mutant protein to cells, which then express the gene and thereby induce an immune response. ‘Understanding how adenoviruses combine and separate could lead to more stable vaccines.’

Documentation source:

Materials provided by the University of Groningen. Note: Content can be edited for presentation and length.

References:

1. Physics of viral dynamics.

Robijn F. Bruinsma, Gijs JL Wuite, Wouter H. Roos. Nature Reviews Physics, 2021;

DOIs: https://www.nature.com/articles/s42254-020-00267-1

The article is translated and edited by ykhoa. org – please do not reup without permission!

Source: ScienceDaily

Links: https://www.sciencedaily.com/releases/2021/01/2101141130130.htm

Translator: Roxie Duong

Editing: Duong Ngoc

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