Informace o projektu

Structural studies of human and animal pathogens from the order Picornavirales

Kód projektu
3041
Období řešení
1/2015 - 12/2020
Investor / Programový rámec / typ projektu
EMBO (European Molecular Biology Organization)
Fakulta / Pracoviště MU
Středoevropský technologický institut

Numerous viruses from the order Picornavirales cause disease in humans
(picornaviruses) or are economically important pathogens of honeybee
(iflaviruses and dicistroviruses). We propose to study molecular structures
of representative viruses from these families and their life cycle intermediates in order to provide mechanistic description of genome
replication and virion assembly. In addition, our results will lay the
foundations for structure-based development of antiviral drugs. We will use X-ray crystallography to determine virion structures of representative picornaviruses from parechovirus and kobuvirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. We will combine high-resolution cryo-EM studies of the replication and assembly complexes prepared in vitro with in vivo analyses of corresponding complexes in the context of infected cell in order to corroborate biological relevance of our structural findings. Furthermore, we will study structures of virions and non-structural proteins of honeybee pathogens Deformed Wing Virus and Israeli Acute Paralysis Virus from families iflaviridae and dicistroviridae, respectively. A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography at previously unprecedented resolution. Our analysis of virion structure, genome replication, and particle assembly will identify molecular details and mechanism of function of critical virus life-cycle intermediates.

Publikace

Počet publikací: 8