Rotaviruses kill over 170,000 children each year, and vaccines only partially protect in some regions. These unique viruses carry exactly eleven RNA chromosomes that must be precisely packaged – a process that drives both the assembly of virions, as well as the emergence of new strains. Our research explores how rotaviruses assemble their genomes, aiming to uncover the mechanisms behind viral evolution and reassortment, with the goal of guiding the development of more effective vaccines and therapies.
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Immunofluorescence imaging of rotavirus replication factories (viroplasms) in infected cells visualised using anti-NSP5 antibodies (red). Inset – electron micrograph of viroplasms filled with newly formed viral particles (arrows).
Biomolecular condensates of purified rotaviral proteins NSP5 (green) and the RNA chaperone NSP2 (magenta) formed spontaneously in vitro. NSP5 and NSP2 form protein droplets that resemble viroplasms in rotavirus-infected cells, allowing us to study how RNA viruses may exploit protein-RNA condensates for their replication.
Our research explores how rotaviruses, a major cause of severe diarrhoeal disease in children, assemble and evolve. Despite vaccines, these viruses continue to cause significant illness worldwide, and no specific antiviral treatments exist.
Rotaviruses contain 11 RNA segments that must be accurately packaged to form infectious virus particles. This complex genome organisation allows the virus to evolve through reassortment, where RNA segments are exchanged between strains to create new variants. The precise mechanisms of RNA segment selection and packaging remain largely unknown.
Using advanced single-molecule fluorescence imaging, biophysical tools, and RNA biology techniques, our team investigates how rotavirus genomes are assembled. By understanding how individual RNA segments interact and are incorporated into new viruses, we aim to uncover the fundamental principles behind viral assembly and evolution.
Our ultimate goal is to translate these discoveries into improved vaccines and antiviral strategies, tackling a major global health challenge and helping protect children worldwide.
2024
Phase separation and viral factories: unveiling the physical processes supporting RNA packaging in dsRNA viruses
Haller, C., Acker, J., Arguello, E.A., Borodavka, A.
Biochem Soc Trans – 52(5):2101-2112.
2023
Principles of RNA recruitment to viral ribonucleoprotein condensates in a segmented dsRNA virus
Strauss, S., Acker, J., Papa, G., Desirò, D., Schueder, F., Borodavka, A., Jungmann, R.
Elife – 12:e68670.
2021
Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses
2. Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W.E., Saar, K.L., Erkamp, N.A., Qi, R., Bravo, J.P.K., Strauss, S., Krainer, G., Burrone, O.R., Jungmann, R., Knowles, T.P.J., Engelke, H., Borodavka, A.
EMBO J. – 40(21):e107711.
2021
Structural basis of rotavirus RNA chaperone displacement and RNA annealing
Bravo, J.P.K., Bartnikm K., Vendittim L., Ackerm J., Gailm E.H., Colyer, A., Davidovich, C., Lamb, D.C., Tuma, R., Calabrese, A.N., Borodavka, A.
Proc Nat Acad Sci – 118(41):e2100198118.