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13. Dec. 2021
Press release, 13.12.2021
A team of scientists led by Robert Vácha from CEITEC Masaryk University (MU) made another important discovery. The researchers combined their know-how in the field of structural virology and computer simulations and managed to describe how genetic information is released from viral particles. They described several ways of releasing the viral genome and were able to describe how the properties of the viral particles determine the process of genome release. The results of their research were published in the American Chemical Society journal ACS Nano and their image was showcased on the cover of the December issue of the journal. (IF 15.8).
Nowadays, we think about viruses almost daily. We are especially interested in the symptoms of viral infections that bother us when we have a flu, cold, or covid-19. But scientists are most interested in the processes that take place in our body when a virus attacks. If we want to defeat an enemy, we need to know exactly how is he striking. At the cellular level, viral infection is manifested by the multiplication of the virus in the infected cells, the following death of the cell, and the subsequent infection of other healthy cells. To start a viral infection, the viruses must first enter the cells and release their genetic information. The research team from CEITEC focused on describing the process of the release of genetic information (genome / RNA) from viral particles and how the various properties of viral particles determine the mode of genome release.
The experimentally captured structures of this process, which have been known so far, have indicated different ways of releasing the genome from the virus. However, it was not clear why different viruses release their genomes in different ways and by what mechanisms are behind it. Initially, researchers hypothesized that viral genetic information escapes slowly through gaps in a protective envelope called a viral capsid. However, there are also capsids without gaps, which still allow for the release of genetic information. "Our recent results have shown that viral capsids can suddenly open and the genome could escape quickly. In this publication, we have shown that both ways are possible and we were able to determine how the physical properties of the capsid determine which of the genome release methods from the virus will be the main one, "describes the first author of the study Lukas Sukenik from Robert Vacha's research group.
"If we understand how the genome is released from the virus at the molecular level, other research teams can use this knowledge to develop antiviral drugs. For example, by attaching to the viral capsid and disabling its opening, or by making the genome release more difficult. In addition, our findings could be used for the targeted delivery of drugs to the cells using virus-like capsids that could increase the drug's effectiveness while reducing its side effects,” explains Robert Vacha the impact of his discovery.
"The research team made this discovery thanks to a combination of computer simulations and cryo-electron microscopy technology. Pavel Plevka's research group used an electron microscope to obtain unique static images of viruses at the exact moment of their genome release. "However, electron microscopes cannot capture the dynamics of the genome release from the virus," explains structural virologist Pavel Plevka, whose research group contributed to the discovery.
"That's why we developed a new computer model of the virus based on structures previously determined by electron microscopy. Subsequent simulations of genome release complemented the electron microscopy images and provided a time perspective, which revealed various possible ways of opening the viral capsid. Thanks to changes in the capsid model, we determined the influence of different physical properties of the capsid on the way genetic information is released,” adds Robert Vacha.
All simulations and their analyses leading to this discovery were performed by the talented doctoral student Lukas Sukenik from the research group of Robert Vacha. Liya Mukhamed, Michaela Prochazkova and Karel Skubník are behind other important experiments that come from Pavel Plevka's structural virology research group. This research was funded by the Grant Agency of the Czech Republic and projects supported by the Ministry of Education, Youth and Sports.