This is part of the Principal Investigator Seminar Series.
Enteroviruses, the causative agents of diseases ranging from the common cold to poliomyelitis, are one of the largest groups of non-enveloped viruses. To initiate infection, most enteroviruses enter cells by receptor-mediated endocytosis. However, it remains unknown how enterovirus particles release their genomes and ensure that the virus RNA reaches the cytoplasm.
We show that expansion of enterovirus RNA genomes, induced by acidic pH in endosomes, triggers the opening of enterovirus particles. The exit of the RNA from the enterovirus particle results in a loss of a few adjacent capsid-protein pentamers. The opening in the capsid, 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. Furthermore, we used cryo-electron tomography of infected cells to show that endosomes containing enteroviruses deform, break open, and release the virus particles into the cytoplasm. Endocytosis of very-low-density lipoprotein, the natural substrate of rhinovirus 2 receptor, results in disruption of endosomes similar to that of enterovirus-containing endosomes. In combination, our results show that enterovirus receptor binding and endocytosis activate a cellular membrane remodeling pathway that disrupts the virus-containing endosomes and thus releases the virus particles and genomes into the cytoplasm.
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