Rotavirus that causes gastroenteritis in humans is divided into three groups called groups A, B, and C. Both A and C mainly affect children and are the most studied and characterized. On the other hand, little is known about the spike protein of group B, which causes severe diarrhea in adults.
According to Phys.org, group B's spike protein known as VP8* domain mediates the infection of cells in the gut. Corresponding author Dr. B. V. Venkataram, a professor at Baylor College of Medicine, said that determining the structure of VP8* is important in understanding how rotavirus infects gastrointestinal cells and designing therapeutic methods against the infection.
Determining the 3D Structure of VP8*
The news outlet reported that the first step in determining the 3D structure of VP8* in group B is using X-ray crystallography. However, it is a laborious and time-consuming process. The traditional approach was unsuccessful at this time. So, researchers turned to a newly-developed artificial intelligence (AI) called AlphaFold2.
Biochemistry and molecular biology Professor Dr. Liya Hu from Baylor, who is also the first author and co-corresponding author of the study, explained that AlphaFold2 could predict the 3D structure of proteins based on their genetic sequence.
She added that the VP8* of rotavirus group B is 10% similar to the sequences of VP8* for groups A and C, so it is expected that there will be differences in its structure in 3D. However, they were surprised when that was not the case.
In the study "Novel Fold of Rotavirus Glycan-Binding Domain Predicted by AlphaFold2 and Determined by X-Ray Crystallography," published in Communications Biology, researchers reported that the AI predicted a 3D structure that was not totally different from the VP8* of groups A and C. Also, there has been no other protein before that has its structure.
Given this information, the researchers went back to the traditional approach using X-ray crystallography to confirm the structure of Vp8* in rotavirus group B. The findings showed that AlphaFold2 correctly predicted the protein's actual structure.
Differences in How Rotavirus Groups Infect Cells
Past studies have shown that the three groups of rotavirus infect gastrointestinal cells differently. For instance, groups A and C use the VP8* domain to bind to specific sugar components in histo-blood antigens, such as blood types A, B, AB, and O, which are present in many cells of the body.
According to a similar report from News Medical Life Sciences, the differences in how rotavirus groups infect cells or bind to different sugars in histo-blood antigens might explain why some viruses infect young children and affect other populations. But unlike VP8* domain rotavirus groups A and C, the VP8* domain in group B had not been characterized not until now.
Hu said that the 3D structure showed them that group B could recognize N-acetyllactosamine, a common sugar found in the body but something that groups A and C do not recognize. She added that the 3D structure also showed that it is capable of recognizing sugar that has never before been identified.
Now that they have determined the 3D structure of VP8* in rotavirus group B, the team is planning to grow them in the human organoid systems, which will help them probe the mechanism of the virus entry and growth. They hope that this will lead to new therapeutics and treat gastrointestinal diseases.
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