PUBLICATION HIGHLIGHT
A key first step in rotavirus infection
This publication highlight is part of the SBGrid/Meharry Medical College Communities Project, focused on science education and demonstrating how structural biology and preclinical science connect to medicine.
Rotavirus is one of the most common viruses that infects children under 5 across the globe. Typical symptoms of a rotavirus infection include vomiting, fever, gastroenteritis (inflammation of the digestive system), and diarrhea, which can lead to severe dehydration and the need for hospitalization. Despite the availability of a vaccine, rotavirus is still the most common cause of gastroenteritis-related hospitalizations for children in the United States.
RNA viruses are clever. Most infect human cells by inserting their genetic material, which is RNA because they do not have DNA like humans and animals. In addition to inserting RNA, these viruses also insert a special protein called RNA-dependent RNA polymerase into the cells. This RNA-dependent RNA polymerase tricks the human cell by hijacking all molecules in the human cell, a process that enables the virus to make copies of itself. Once it replicates, the RNA virus destroys the human cell. With multiple copies of the RNA virus able to infect more human cells, it can rapidly lead to cell death and become problematic, especially in children.
Rotaviruses, and other double-stranded RNA viruses, are distinctive because they deliver their RNA and RNA-dependent RNA polymerases by inserting them as a large particle into the cell. This large particle is called a double-layered particle. The double-layered particle is wrapped around another set of proteins creating a triple-layered particle that helps ensure the double-layered particle makes it into the cell. How the proteins that make up the triple-layer particle work to help the double-layered particle get into the cell was a mystery.
SBGrid member Steven Harrison and colleagues showed in their work titled, The rotavirus VP5*/VP8* conformational transition permeabilizes membranes to Ca2+, the key steps needed for rotavirus infection. Their results show that VP5*/VP8, proteins that make up part of the triple-layered particle, are able to change their shape. This change in the three-dimensional shape, also known as a conformational change, causes VP5*, VP8*, and another outer layer protein, VP4, to insert a portion of their back end or C-terminus into the cell membrane. This process makes the cell membrane a bit looser to allow for insertion of the viral particle. The cell membrane’s weakened permeability is due to a calcium “leak” that is created from a portion of the triple-layered particle inserting itself into the membrane. Understanding this process, the first step in helping the double-layered particle successfully get inside cells and cause infections, can provide the foundation for novel therapies to reduce hospitalization of children infected by rotavirus throughout the world.
Read more in PLOS Pathogens.
By KeAndreya Morrison, Meharry Medical College
KeAndreya Morrison is a biomedical sciences Ph.D. Candidate at Meharry Medical College studying the relationship between host and pathogen through the lens of structural biology. KeAndreya is a Georgia native where she completed her bachelor’s degree in biology at Fort Valley State University in Fort Valley, GA.
