While we already have a good view on the structure of viruses, it remains an open question what the actual process of assembly looks like. Physicists have now unveiled this by following the viral assembly process “live”. This challenge was made possible by looking at one single DNA molecule, suspended in liquid using a so-called optical tweezer. By immobilising the DNA in this manner, it was possible to follow the addition of the viral proteins, one-by-one. Herewith, not only the first steps of assembly were laid bare, but also the subsequent growth process.
The researchers from Mexico, Eindhoven, Wageningen, Amsterdam and Groningen used a technique for which the 2018 Nobel prize in Physics was awarded: Optical tweezers. With this technique a DNA molecule can be caught in between two glass beads using strongly focused laser beams. By adding fluorescent proteins from an artificial virus, these proteins attached to the DNA and started to pack the DNA inside the growing protein structure. The figure visualizes this process. Zernike group leader and last author Wouter Roos: ,,The nice thing of this technique is that one cannot only see where the viral proteins are attaching, but that one can also measure the force with which packaging occurs. This allows for both a detailed visualization and quantification of the viral assembly process.’’ The experiments were supported by other advanced techniques such as acoustic force spectroscopy and atomic force microscopy. The former is a technique in which glass beads are trapped using sound waves (instead of light), and in the latter technique a tiny needle is used to make a topographic map of very small structures, such as assembling viruses. By combining the data of these three techniques, the researchers were able to establish that the DNA packaging occurs with very small, but regular steps.
These novel findings enlighten the viral assembly process, but also directly raise the question whether this is a general mechanism. Further research on different particles will be able to shed more light onto this question. This work does not only generate new fundamental insights. By better understanding how viruses are built up, the search for anti-viral drugs that specifically target certain steps in assembly is also facilitated.
Margherita Marchetti, Douwe Kamsma, Ernesto Cazares Vargas, Armando Hernandez García,
Paul van der Schoot, Renko de Vries, Gijs J. L. Wuite, and Wouter H. Roos
Real-Time Assembly of Viruslike Nucleocapsids Elucidated at the Single-Particle Level
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