New research from University of California Santa Cruz biologists shows how antibodies work to stop astrovirus infections, offering a potentially new way to develop a vaccine and treatment for this infection.
Astrovirus is one of the most common causes of childhood acute diarrhea. While it’s not considered a serious condition in healthy children, the virus can cause more serious illness in children with cancer and compromised immune systems. However, now a new study on the structure of its viral protein shell provides additional insight on how researchers may be able to develop therapies and vaccines for human astrovirus.
Viral gastroenteritis, or the stomach flu, is often caused by astrovirus, as well as rotavirus, norovirus, and calicivirus. Astrovirus infections are marked by symptoms such as diarrhea, vomiting, abdominal cramping, headache, fever, and mild dehydration. Cases of astrovirus are generally milder than other intestinal infections and less likely to require hospitalization; those who are mostly commonly affected are children under the age of 2 years. Childhood infection allows the immune system to develop antibodies to the virus early in life, offering protection against further infection in adulthood. However, for immunocompromised children and adults, such as those living with cancer or HIV, along with elderly individuals with waning immunity, astrovirus can cause more severe and chronic gastroenteritis.
There are currently no antiviral treatments to target astrovirus infections nor vaccines to prevent them, but a recent study from researchers from the Unversity of California in Santa Cruz looked at the structure of the astrovirus itself and how antibodies work to block the virus in healthy adults. Their paper was recently published in the American Society for Microbiology’s Journal of Virology. In it, the authors noted that by the age of 10, about 75% of children in the United States have acquired antibodies against human astrovirus due to infection, and that healthy adults who have no astrovirus antibodies due to lack of previous infection can develop severe diarrhea. For children with immunocompromised conditions, astrovirus can be challenging, said study author Rebecca DuBois, PhD, something she had observed during her time working in a children’s hospital. "There were all these young cancer patients who were successfully fighting their cancer, but they were getting severe chronic astrovirus infections because the chemotherapy suppressed their immune systems, and there was no treatment for it," explained Dr. DuBois in a recent press release.
The viral particles of the astrovirus have a protein shell called a capsid, and the research team used x-ray crystallography to determine that astrovirus antibodies bind to a structure called a capsid spike domain, which extends from the surface of the virus. Antibodies work by binding to the spike domain and preventing virus cells from attaching to and infecting human cells. With this finding, the team has discovered a new path for the development of both a vaccine to prevent the virus as well as a possible treatment for active infections.
“This study reveals that a virus-neutralizing antibody — an antibody that blocks the virus from infecting cells – targets a specific fragment or subunit of the astrovirus surface,” Dr. DuBois explained to Contagion. “Thus, we have identified an ‘Achilles' heel’ on the virus. With this information, we can now move forward to develop a subunit vaccine comprised of just that fragment of the virus, and immunizing a person with this fragment would elicit virus-neutralizing antibodies that would prevent virus infection in that person. This study also suggests the possibility of treatment by ‘artificial immunity,’ where a person with a severe or chronic astrovirus infection would be treated with a lab-made virus-neutralizing antibody.”
While much progress needs to be made for many deadlier and more serious diseases, there are many advantages to developing ways to prevent and treat astrovirus infections, according to Dr. DuBois. “Although astrovirus infections do not have the same severity or hospitalization rates as other viruses, they still cause significant disease — such as diarrhea, vomiting, and fever – that is taking children out of school and taking parents out of work,” Dr. DuBois noted. “Moreover, infected individuals spread astrovirus to the most susceptible members of our population, including infants, preemies, elderly, and immune-compromised individuals, who often end up with more severe and chronic infections of astrovirus. Thus, I do think a vaccine would benefit our society and should be recommended for children.”