Informace o projektu
Mechanism of Viral Genome Release (VirGenEx)

Last century saw an accelerating trend in emergence or resurgence of human pathogens. The deadliest diseases are almost exclusively caused by viruses, and have a high potential to reach pandemic status, as demonstrated by HIV/AIDS and influenza A outbreaks. Increased incidence was linked to demographic and environmental factors such as high population density, increased migration, economic transition and climate change. As a result, the European area has been identified as a hot-spot for the emergence of infectious diseases. While immunization proved to be an effective strategy against some virus-caused diseases, many viral pathogens exhibit high mutation and recombination rates allowing them to rapidly escape vaccines and treatments. It has been suggested that effective anti-viral therapies will require a combination of approaches, targeting simultaneously at least three different stages of viral life-cycle. It is therefore crucial to close the substantial knowledge gaps in our understanding of viral life-cycle and pathogen-host interaction. To further this objective, this project aims to elucidate viral genome organization and the mechanism of its release into host cells, employing a combination of biochemical and biophysical approaches allowing a description of this process at an atomic-level of detail. Contrary to the high degree of symmetry of viral capsids, the packaged or exiting genomes do not follow icosahedral symmetry rules.
Consequently, structural approaches relying on icosahedral averaging could provide only inadequate information about their arrangement. However, recent studies employing asymmetric particle reconstruction from cryo-electron microscopy data demonstrated the maturity of this approach for determination of high-resolution structures of non-symmetric viral features.