Organelle-Like Membrane Compartmentalization of Positive-Strand RNA Virus Replication Factories

Positive-strand RNA virus genome replication is invariably associated with extensively rearranged intracellular membranes. Recent biochemical and electron microscopy analyses, including three-dimensional electron microscope tomographic imaging, have fundamentally advanced our understanding of the ultrastructure and function of organelle-like RNA replication factories. Notably, for a range of positive-strand RNA viruses embodying many major differences, independent studies have revealed multiple common principles. These principles include that RNA replication often occurs inside numerous virus-induced vesicles invaginated or otherwise elaborated from a continuous, often endoplasmic reticulum-derived membrane network. Where analyzed, each such vesicle typically contains only one or a few genome replication intermediates in conjunction with many copies of viral nonstructural proteins. In addition, these genome replication compartments often are closely associated with sites of virion assembly and budding. Our understanding of these complexes is growing, providing substantial new insights into the organization, coordination, and potential control of crucial processes in virus replication.