Endomembrane mutiny: how picornaviruses hijack host organelles to support their replication

Melia, C.E. (2019)

Doctoral Thesis

Replication organelles (ROs) are novel membrane rearrangements formed in the host cell cytosol during infections of positive-sense RNA (+RNA) viruses, which are utilised as platforms for viral replication. This thesis addresses several open questions regarding the ROs of picornaviruses, including the host factor requirements for enterovirus RO formation, their potential functions, and the on-going uncertainty surrounding their origin. It extends our detailed understanding of enterovirus ROs to a second picornavirus genus, the cardioviruses, with broader ramifications for the development of antiviral strategies. The resulting data highlight an unexpected degree of flexibility in the use of membranes for vRNA synthesis, asking for a re-examination of how we define the replication organelles of +RNA viruses.

• Picornaviruses
• Enteroviruses
• Cardioviruses
• Replication organelles
• Phosphatidylinositol 4-phosphate
• Electron microscopy
• Light microscopy
• Correlative light and electron microscopy

• All authors: Melia, C.E.
• Supervisor: Koster, A.J.; Kuppeveld, F.J.M. van
• Co-supervisor: Bárcena, M.
• Committee: Snijder, E.J.; Akhmanova, A.; Hoeben, R.C.; Smit, J.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-05-21
• ISBN (print): 9789463324977
• Sponsorship: Section Electron Microscopy