Thursday 21 January 2021

Physical virology shows the dynamics of virus reproduction

The reproductive cycle of viruses requires self-assembly, maturation of virus particles and, after infection, the release of genetic material into a host cell. New physics-based technologies allow scientists to study the dynamics of this cycle and may eventually lead to new treatments. 

The laws of physics govern important events in their reproductive cycle. 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 sub-second time resolution. 

Viruses hijack cells and force them to make the protein building blocks for new virus particles and to copy their genetic material (either RNA or DNA). This results in a cellular soup full of virus parts, which self-assemble to produce particles of encapsulated RNA or DNA.

No external energy is required for this process. And even in vitro, most viruses will self-assemble quickly. This process was traditionally studied in bulk material, averaging out the behaviour of large numbers of virus particles. 

Over the last few years, technologies have been developed to study these individual particles in real-time. One of those is fast Atomic Force Microscopy (AFM). An atomic force microscope scans surfaces with an atom-sized tip and is therefore able to map their topology. 

Single-molecule fluorescence is also used to study viruses, for example, the attachment of viral proteins to DNA. 

Using optical tweezers, researchers can hold two tiny beads on either end of a DNA molecule. When viral proteins bind to the DNA, this will coil up and bring the two beads closer together. This is visualized by fluorescent markers attached to the beads.

Alternatively, proteins with fluorescent markers can be observed while they attach to viral DNA or to other proteins. A third technology is to use an optical microscope to measure interference of light that is scattered by virus particles. These patterns reveal the structure of the particles during assembly. 

Other steps in the virus cycle can also be studied. New technology is now revealing the physical dynamics of viruses. It allows scientists to study how genetic material is incorporated and which physical principles guide this process. Most antiviral drugs disrupt the first steps in infection, such as the binding of virus particles to their host cells. Using this new dynamic information, we could develop drugs that block self-assembly or other important steps in the reproductive cycle of the virus. 

Insight into the physics of virus particles is also important for their use in research, for example as building blocks in nanotechnology or as carriers for antigens in vaccines. Several of the leading COVID-19 vaccines use adenoviruses to deliver the gene for the SARS-CoV-2 spike protein to cells, which then express this gene and consequently generate an immune response.


Robijn F. Bruinsma, Gijs J. L. Wuite, Wouter H. Roos. Physics of viral dynamics. Nature Reviews Physics, 2021; DOI: 10.1038/s42254-020-00267-1

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