First Visualization of Entire Cell-Entry Process for Nonenveloped Virus Published in Science

The entire process by which a nonenveloped virus penetrates and enters a cell has been visualized for the first time.

According to BioOn on the 24th (local time), the de Sautu research team published findings in the journal Science using cryo-electron tomography to observe how rhesus rotavirus enters cells.

Viruses are classified as enveloped, with an outer lipid membrane, or nonenveloped, without one. Nonenveloped viruses must penetrate the cell membrane directly using surface proteins, making entry difficult.

Rhesus rotavirus is a double-stranded RNA virus and a major cause of severe diarrhea in infants and young children. The team analyzed the entire process, from the virus attaching to and being taken up by a cell to the release of subviral particles, by linking high-resolution structural data with time-series fluorescence microscopy data from living cells.

The results showed that viral surface proteins trigger two successive rounds of membrane insertion and calcium influx. The first event induces viral uptake into the cell (endocytosis), while the second promotes viral particle maturation and creates a pore in the endosome surrounding it.

The team said the findings could lead to drug development approaches that inhibit membrane insertion or disrupt calcium flow before viral replication begins. They also said the findings could help with the design of effective vaccine antigens.

Other nonenveloped viruses, including enteroviruses and reoviruses, face similar challenges in entering cells, so the mechanism could inform broad-spectrum antiviral strategies, the team said.

Rotavirus causes many deaths among infants and young children each year, particularly in low-income countries. The team hopes that understanding the entry mechanism will lead to the development of drugs, vaccines and precise intervention tools that could reduce the global burden of diarrheal disease in children.