Human astroviruses may lead to
diarrhea, vomiting, and fever. Astrovirus infections affect nearly everyone during childhood, For most people, it's not a serious
disease, but structural biologist Rebecca DuBois saw how devastating it
can be when she worked at St. Jude Children's Research 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," said DuBois, now an assistant professor
of biomolecular engineering at UC Santa Cruz.
‘A site of vulnerability on the surface of the astrovirus that can now be targeted for development of a vaccine or antiviral therapy has been identified by researchers.’
By studying the astrovirus capsid, the protein shell of the viral
particles, the DuBois lab is laying the foundation for new antiviral
therapies and vaccines for human astroviruses. In a new study accepted
for publication in the Journal of Virology
, she used x-ray
crystallography to show how a specific protein structure on the surface
of the virus is blocked by a neutralizing antibody, thus preventing the
virus from infecting human cells.
"We've identified a site of vulnerability on the surface of the
virus that we can now target for development of a vaccine or antiviral
therapy," DuBois said. "These are the first results showing how a
neutralizing antibody blocks this virus."
The study shows how the antibody binds to a structure known as the
astrovirus capsid spike domain, which projects from the surface of the
virus. By binding to the spike domain, the antibody blocks the virus's
ability to attach to and infect human cells.
The new findings provide a roadmap for researchers to design a
vaccine based on the spike domain that can induce neutralizing
antibodies and prevent infection in children. The study also highlights
the potential to develop therapeutic antibodies to treat severe
"Antibody therapeutics is a rapidly growing field. Many
immunotherapies are being developed to target cancer cells, and we
expect to see a growing number of antibody therapies for infectious
diseases over the next ten years," DuBois said.
Graduate student Walter Bogdanoff is first author of the paper.
DuBois noted that the first three authors of the paper - Bogdanoff and
undergraduates Jocelyn Campos and Edmundo Perez - have all been
supported by the STEM Diversity Programs at UC Santa Cruz.
"It's a great program that funds undergraduates and graduate
students from diverse backgrounds to do laboratory research, and they
really do become accomplished scientists and well prepared for graduate
school and careers in science," she said.