Insight into calicivirus replication complex formation

EUVIRNA ESR-8

Project description
RNA viruses with a positive oriented genome rely for replication on cellular membranes interacting with the viral replication complex. Replication of calicivirus that bear a positive oriented genome is presumed to occur in a similar manner. This working hypothesis is of high relevance for elucidating the replication strategy of those important pathogens, paving the way for the development of innovative antiviral approaches targeting the replication complex and more particularly the interaction of this complex with cellular factors. In order to investigate this working hypothesis, a surrogate of the calicivirus that can be cultivated in vitro, the murine norovirus and the feline calicivirus will be used, Both viral strains have been successfully propagated in cell culture systems, and partial aspects of their replication strategy understood. The experimental approach aims using reverse genetics systems as well as molecular methods of genome engineering at mapping viral protein domains, in particular of non structural viral proteins such as helicase, the RdRp or the VPg, as well as additional proteins with so far unknown functions that may potentially interact with cellular membranes. In a further step, a 3D-Model of norovirus and feline calicivirus replication complex will be modelled using Cryo-EM, allowing us to draft the first schemes on the architecture of the replication complex of those medical relevant pathogens.

Host institute
Riboxx GmbH
c/o Institute of Virology,
Dresden University of Technology
Medizinisch-Theoretisches Zentrum
Dresden, Germany
Supervisor: Dr. Jacques Rohayem

Position Filled