Researchers at Baylor College of Medicine have reported a significant advancement in the study of human norovirus, a major cause of acute viral gastroenteritis worldwide. The findings, published in Science Advances, address a long-standing challenge: the difficulty of growing and maintaining norovirus in laboratory settings.
Norovirus poses severe health risks, especially to young children, older adults, and people with weakened immune systems. There are currently no approved vaccines or antiviral treatments for this virus; management relies on supportive care such as fluid and electrolyte replacement.
The main obstacle for researchers has been the inability to grow sufficient quantities of the virus for extended studies. Previous methods allowed limited replication before viral growth would stop, making it hard to develop consistent stocks for research purposes. As a result, scientists had to rely on viruses obtained from patient stool samples, which are inconsistent and limit large-scale experiments.
“In 2016, a previous breakthrough occurred when scientists in our lab and collaborators successfully grew HuNoV in human intestinal enteroids (HIEs), or ‘mini-guts’– miniature, lab grown versions of the human gut,” said first author Gurpreet Kaur, graduate student in molecular virology and microbiology at Baylor working in Dr. Mary Estes’ lab. “While this system allowed researchers to infect cells and study the virus, it still had a major shortcoming – the virus would not grow through repeated rounds, the way scientists can grow many other microorganisms. After just a few rounds, norovirus replication would stop, making it impossible to build up long lasting viral stocks.”
To address this limitation, Baylor researchers examined different versions of HIEs using RNA sequencing to understand why norovirus growth usually stops. “Looking to overcome this obstacle, we studied several versions of HIEs to understand why norovirus growth usually stops,” said co-author Dr. Sue Crawford, assistant professor of molecular virology and microbiology at Baylor. “Using RNA sequencing, a method that measures gene activity, we discovered that infected HIEs produced high levels of chemokines, molecules that help the body mount an immune response. Three chemokines stood out: CXCL10, CXCL11 and CCL5.”
The team then tested whether blocking these chemokine signals could enhance viral replication by using TAK 779—a drug originally developed to block chemokine effects—in their cultures. “We then investigated whether blocking signaling of these chemokines through their receptors would allow human norovirus to replicate better in HIEs,” Kaur said. “We tested a drug called TAK 779, originally developed to block chemokine effects. When TAK 779 was added to the HIE cultures, norovirus replication increased dramatically – virus spread throughout the cells in the cultures, and we achieved replication for 10 to 15 consecutive passages.”
“TAK 779 allowed us to generate consistent batches of infectious virus from lab cultures instead of human stool — something we and other researchers have been seeking for decades,” Crawford said.
However, not all strains responded equally well; TAK-779 enhanced replication primarily for certain strains such as GII.3 but did not improve growth for GII.4 strains—the most common cause of outbreaks—because those did not trigger chemokine secretion during infection.
“We observed that TAK 779 did not enhance replication of GII.4 strains, the most common cause of human outbreaks,” said corresponding author Dr. Mary K. Estes at Baylor College of Medicine’s Department of Molecular Virology and Microbiology as well as other roles within affiliated centers at Texas Medical Center Digestive Diseases Center and Dan L Duncan Comprehensive Cancer Center.“This difference appears to be because GII.4 viruses do not trigger chemokine secretion in HIEs meaning there’s no chemokine response for TAK 779 to block.This suggests that a different process limits GII .4 growth in HIEs.We are currently optimizing our HIE culture conditions enable efficient passaging additional HuNoV strains including GII .4.”
With this new approach allowing continuous cultivation without relying on patient samples,researchers can now conduct more comprehensive studies into viral structure,vaccine development,and antiviral drug screening—even outside specialized labs.Baylor College Medicine continues its mission advancing research ,education ,and community service as an independent health sciences university while engaging clinical partnerships official website. Paul Klotman serves as president ,chief executive officer ,and executive dean official website .
For further details regarding authorship or funding,the full publication is available online.
