Mechanosensitive extrusion of Enterovirus A71-infected cells from colonic organoids

Enterovirus-infected cells are extruded from the apical surface of differentiated human colon organoids by a mechanical-force-dependent mechanism that preserves the uninfected host epithelium. Enterovirus A71 causes severe disease upon systemic infection, sometimes leading to life-threatening neurological dysfunction. However, in most cases infection is asymptomatic and limited to the gastrointestinal tract, where virus is amplified for transmission. Picornaviruses have previously been shown to exit infected cells via either cell lysis or secretion of vesicles. Here we report that entire Enterovirus A71-infected cells are specifically extruded from the apical surface of differentiated human colon organoids, as observed by confocal microscopy. Differential sensitivity to chemical and peptide inhibitors demonstrated that extrusion of virus-infected cells is dependent on force sensing via mechanosensitive ion channels rather than apoptotic cell death. When isolated and used as inoculum, intact virus-containing extruded cells can initiate new infections. In contrast, when mechanical force sensing is inhibited, large amounts of free virus are released. Thus, extrusion of live, virus-infected cells from intact epithelial tissue is likely to benefit both the integrity of host tissues and the protected spread of this faecal-oral pathogen within and between hosts.

Automated summary

Infected cells in the human colon tissue are extruded through a mechanism that depends on mechanical force, which helps maintain the integrity of the uninfected host epithelium. In the case of Enterovirus A71, infected cells are specifically extruded from the apical surface of differentiated human colon organoids using mechanosensitive ion channels, rather than undergoing apoptotic cell death. These extruded cells can be used as a source of virus for new infections.