Packaging of Single-Stranded RNA in Viruses and Virus-Like Particles

Our double-stranded DNA (dsDNA) genomes are famously compacted by proteins in the nuclei of our cells, resulting in meters of dsDNA being confined in micron-sized volumes. The most prevalent form of viral genomes, however, is single-stranded RNA (ssRNA), which is compacted at significantly higher density in protective protein shells with nanometer dimensions. In this review, we discuss the special nature of ssRNA that allows it to be spontaneously packaged in this way by co-self-assembly with viral capsid protein (CP). We focus on the few viruses whose nucleocapsids can be reconstituted from their purified CP and ssRNA genomes and whose CPs can spontaneously package heterologous RNA into virus-like particles (VLPs). These VLPs are then compared with their cell-synthesized versions, with lentivirus and adeno-associated virus vector particles, and with nucleocapsids formed by nonviral proteins whose messenger RNAs are put under directed evolutionary pressure to be packaged by them in cellulo.