Enteroviruses from the family Picornaviridae are human pathogens that cause a range of diseases from the common cold to severe brain inflammation. Despite the societal and economic impact of enteroviruses, the available treatments are only symptomatic. The enterovirus cell entry and the release of the viruses from endosomes are potential targets for antiviral therapeutics. However, the details of these phenomena are not well understood.
Here, we used in situ cryo-electron tomography to visualize the cell entry and genome release of human rhinovirus 2. We observed endosome membrane remodelling and breakage followed by virus escape into the cytoplasm. We demonstrate that the endosome disruption is mediated by overactivation of a cellular mechanism by showing that endocytosis of very-low-density lipoprotein, the natural substrate of rhinovirus 2 receptor, also results in endosome disruption. The described mechanism of rhinovirus 2 cell entry is supported by data collected on other enteroviruses. Our results give evidence of the cellular mechanisms these viruses employ to enter cell hosts.
We acknowledge the Cryo-electron microscopy and Tomography Core Facility of CEITEC MU for their support in data collection and analysis.