How Viruses and Virus-like Nanoparticles Can Release Their Cargo/Genome

Lukáš Sukeník1,3, Liya Mukhamedova1, Michaela Procházková1, Karel Škubník1, Pavel Plevka1, and Robert Vácha1,2,3

1Central European Institute of Technology (CEITEC), Faculty of Science, Masaryk University, Kamenice 735/5, Brno, Czech Republic

2National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 735/5, Brno, Czech Republic

3Department of Condensed Matter Physics, Faculty of Science, Masaryk University, Kotlářská 267/2, Brno, Czech Republic

robert.vacha@mail.muni.cz


Viruses and virus-like nanoparticles both aim to deliver their content into a cell. Unfortunately, the necessary capsid properties enabling cargo/genome release and the release mechanism itself remains elusive. We combine in vitro cryo-EM experiments with coarse-grained simulations to demonstrate that the cargo/genome can be released in various pathways, including a slow release via small pores in the capsid and a rapid release when the capsid cracks open [1,2,3]. The main capsid property determining the release pathway is the interaction range between capsid subunits. The release success rate depends on the cargo/genome properties, but in general, the rapid release is more successful. These findings indicate how to affect and design the release of cargo/genome from viruses and virus-like nanoparticles.

 

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Figure 1. Two types of genome release from non-enveloped RNA virus: a slow release via small pore in the capsid (left) and a rapid release when the capsid cracks open (right).

 

1. D. Buchta, T. Füzik, D. Hrebík, Y. Levdansky, L. Sukeník, L. Mukhamedova, J. Moravcová, R. Vácha, P. Plevka, Nature Communications, 10, (2019), 1138

2. K. Škubník, L. Sukeník, D. Buchta, T. Füzik, M. Procházková, J. Moravcová, L. Šmerdová, A. Přidal, R. Vácha, P. Plevka, Science Advances 7 (1), (2021), eabd7130.

3. L. Sukeník, L. Mukhamedova, M. Procházková, K. Škubník, P. Plevka, R. Vácha, ACS Nano 15(12), (2021), 19233–19243.

The work of was supported by Czech Science Foundation project no. GA20-20152S and GX19-25982X, MEYS CR via LL2007 project under the ERC CZ program, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 101001470). Computational resources were provided by CESNET LM2015042 and CERIT Scientific Cloud LM2015085, provided under the program Projects of Large Research, Development, and Innovations Infrastructures. Additional computational resources were obtained from the IT4 Innovations National Supercomputing Center -- project LM2015070 supported by MEYS CR from the Large Infrastructures for Research, Experimental Development and Innovations. We gratefully acknowledge the Cryo-EM core facility CEITEC MU of CIISB (CEMCOF), and the Instruct-CZ Centre supported by MEYS CR (LM2018127).