Looking at the nanoworld

Super-resolution microscopy gives new insights into the organization of rotavirus proteins within infected cells.

Comparison between a super-resolution microscopy image of the structure of a rotavirus viroplasm (left) and the traditional immunofluorescence microscopy image (right). Image credit: José L. Martínez, David T. Hernández and Adán Guerrero (CC BY 4.0)

Rotaviruses are small viruses that can infect cells in the intestine. They are responsible for most cases of severe infectious diarrhea, the most common cause of death among young children in developing countries. Controlling the spread of rotavirus infections is difficult, even with high levels of hygiene, so effective treatments are essential to curtail the virus’ infections. Understanding how new rotaviral particles are made in infected cells is one of the first steps toward developing new therapies.

Once rotaviruses enter the cells, proteins from the virus and the cell aggregate into compact spheres called viroplasms to make new viral particles. Studying these viroplasms used to be difficult because they are too small to see with the resolution of standard microscopes. In recent years, advances in microscopy and mathematical methods have focused on breaking the existing resolution limits, leading to the development of super-resolution microscopy. This new technique has made it possible to study objects with sizes in the order of a billionth of a meter, known as nanoscopic structures, including viroplasms.

Garcés et al. use super-resolution microscopy to determine how viral proteins are arranged in the viroplasm and gain a better understanding of how the viruses are assembled. The images revealed that, in infected monkey kidney cells, rotavirus proteins inside the viroplasm form highly organized concentric layers. This arrangement is reliably repeated in viroplasms of different sizes, indicating that the organization of the proteins is likely set up when the viroplasm starts to form.

These findings make use of new microscopy, image analysis and statistical tools to study rotaviruses, providing a new framework to understand many aspects of rotaviral biology. Additionally, the result showing that proteins organize consistently in viroplasms is a first step towards understanding how the machinery that makes new rotaviruses works, which could lead to future treatments for severe infectious diarrhea.