Within infected cells, single-stranded positive-sense RNA (ss(+)RNA) viruses, such as Hepatitis C virus (HCV), establish membranous replication complexes to provide a protective environment for viral RNA replication. A key component of replication complexes is the viral membrane-associated replicase, which catalyzes the amplification of the viral genome.
We use cryogenic electron-tomography (cryo-ET) in combination with advanced image processing to investigate structural characteristics of HCV replication complexes in their native environment, i.e. within cells. Revealing the higher-order assemblies of replicase proteins in complex with the viral RNA in situ allows us to address fundamental concepts of replication complex formation and replicase function.