Behind Closed Membranes: The Secret Lives of Picornaviruses?

If there is one truism that often opens a review or talk about picornaviruses, it is that the entire replication cycle of these simple positive-strand RNA viruses takes place in the cytosol.This statement is usually made to directly contrast picornaviruses with retroviruses or DNA viruses that require transport to the nucleus.However, the statement is meant quite literally.Some enveloped RNA viruses enter organelles to bud from the cellular secretion pathway, while other RNA viruses replicate their genomes in tightly controlled organelle invaginations.In contrast, every step in the replication of picornaviruses, once the genome has entered the cytosol, has long been thought to take place directly in the cytoplasm or on the cytoplasmic face of membranous structures [1].Recently in PLOS Pathogens, we reported that inhibiting acidification of cellular vesicles reduces yield of the type picornavirus, poliovirus, by 90% or more [2].