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10. Aug. 2026
A team from CEITEC Masaryk University (MUNI) in collaboration with researchers from two research institutes in Norway has, for the first time, captured how echovirus 18, a member of the enterovirus genus, releases its genetic material into cells to initiate infection. The study provides a structural view of an early stage of viral infection under near-native conditions. Using cryo-electron microscopy, the researchers discovered that the virus does not release its RNA through a small pore in its capsid, as had long been assumed. Instead, its protein shell partially disassembles, creating a large opening through which the viral genetic material escapes into the host cell. A detailed understanding of this genome release mechanism could eventually help develop compounds preventing enteroviruses from infecting cells.
Enteroviruses are common human pathogens causing diseases ranging from the common cold and gastrointestinal infections to severe neurological disorders. Echovirus 18, the virus investigated in this study, is known primarily as a cause of meningitis and encephalitis in children. It belongs to the picornaviruses, a family of small, non-enveloped viruses whose genetic material is protected by a protein shell, the capsid, organized with icosahedral symmetry.
To replicate within a cell, the enteroviruses must release their RNA – the molecule that carries viral genetic information – from the capsid, into the cell cytoplasm. Although this step is crucial for initiating infection, it has never been observed in infected cells.
“For a long time, two main theories existed about how picornaviruses deliver their RNA genomes into cells. One proposed that the genome leaves the capsid through a small opening. The other, supported by earlier work from our laboratory, suggested that the genome escapes from partially disassembled capsids missing pentamers of capsid proteins. However, both models were based on experiments with virus particles outside cells. We wanted to go one step further and see what really happens during infection inside a cell,” says Liya Mukhamedova, the study’s first author from CEITEC MUNI.
Using cryo-electron microscopy, which allows scientists to visualize biological structures at exceptionally high resolution, the researchers observed individual echovirus 18 particles directly within infected cells. They discovered that empty virus particles in infected cells lack parts of their capsids. It is through these openings that the virus releases its RNA.
The study also revealed the role of the FcRn receptor, a cell-surface molecule that enteroviruses use to enter cells. The binding of the virus to the receptor triggers structural changes in the viral particle that prime it for subsequent genome release. The team showed that receptor binding causes the loss of the so-called pocket factor, a small molecule that normally helps stabilize the virus particle. The virus otherwise remains largely intact, suggesting that receptor binding is only the first step toward uncoating, while additional factors within the cell are required to complete the process and trigger genome release.
“Infection is a complex process, during which enterovirus particles sense various interactions with cell components. The binding of echovirus 18 to the FcRn host-cell receptor triggers conformational changes in the virus, priming it for genome release.” – explains Pavel Plevka, head of the Structural Virology Research Group.
The researchers did not observe the so-called activated particles that are key intermediates in the enterovirus uncoating process. This suggests that genome release in cells occurs much faster than previous experiments had suggested.
By combining structural data obtained from studies of virus particles outside living cells with observations of infected cells, the study offers a picture of how enterovirus infection begins. Moving beyond simplified experiments with isolated virus particles, it brings scientists closer to understanding the earliest stages of enterovirus infection as they occur in living cells. The study, was published in the PNAS journal.
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