Viruses from the genus Enterovirus are important human pathogens. Receptor binding or exposure to acidic pH in endosomes converts enterovirus particles to an “activated” state that is required for genome release. However, the mechanism of enterovirus genome release is not well understood. Here, we used cryo-electron microscopy to visualize virions of human echovirus 18 in the process of genome release.
We discovered that viral RNA exits the echovirus 18 particle through a hole that forms in the capsid upon loss of one, two, or three adjacent capsid-protein pentamers. The resulting hole, which is more than 120 Å in diameter, enables the release of the genome without the need to unwind its putative double-stranded RNA segments. Thus, our findings uncover a novel and conserved mechanism of enterovirus genome release that could become target for antiviral drugs.