University of Heidelberg, Department of Infectious Diseases, Molecular Virology, Centre for Integrative Infectious Disease Research (CIID), Heidelberg, GERMANY

Thursday 14 November 2019 | 12:00 noon – ICGEB Trieste, ITALY

An integrated view of viral replication organelles

Host: A. Marcello

Positive-sense single-stranded RNA viruses, including Flaviviruses such as dengue virus and Zika virus, replicate their genomes within specialized membrane compartments called “viral replication organelles” (ROs). As a consequence of the compact size of their genome and limited coding capacity, these viruses utilize host factors to modify and reshaping both cellular organelles and signaling pathways to form their ROs which facilitate viral genome replication and production of viral particles. For Flaviviruses, these ROs consist of membrane invaginations within the ER lumen that form clusters of vesicles connected to the cytosol by a pore-like opening. This compartmentalization acts to shield the viral replication intermediates from cytosolic innate immune sensors while still allowing exchange of metabolites. However, very little is known about the molecular constituents or mechanisms that regulate RO biogenesis or coordinate different viral processes such as genome replication and particle assembly. Here we use advanced light and electron microscopy techniques to define the structure and molecular mechanisms involved in the formation of the viral ROs. Additionally, we have established correlative light electron microscopy techniques (CLEM) that complement molecular and dynamic parameters of a biological process with ultrastructural characterization, to study different aspect of host-pathogen interactions. Using these integrative approaches we have identified key macromolecular complexes and cellular processes that are involved in the biogenesis of flaviviruses ROs.