Method Developed to Sustain Norovirus Growth in the Lab

Human norovirus (HuNoV) is a primary cause of viral gastroenteritis worldwide, affecting young children, older adults, and immunocompromised individuals most severely. Despite its global impact, no approved treatments or vaccines exist, and current care relies on managing symptoms. For years, scientists have struggled to grow HuNoV consistently in laboratory systems, limiting progress in understanding the virus and developing preventive or therapeutic strategies.

Now, a team from Baylor College of Medicine reports in Science Advances that they have identified factors that restrict viral replication and developed a way to overcome them to optimize long-term viral cultivation.

“In 2016, a previous breakthrough occurred when scientists in our lab and collaborators successfully grew HuNoV in human intestinal enteroids (HIEs), or ‘mini‑guts,’” said first author Gurpreet Kaur. “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.” This limitation forced scientists to rely on HuNoV collected from patient stool samples, which are inconsistent and difficult to obtain in large quantities.

Co‑author Dr. Sue Crawford explained that her team examined multiple HIE models to determine why replication stops. Using RNA sequencing, they found that infected cells produced high levels of certain chemokines—CXCL10, CXCL11, and CCL5—that activate immune responses. The researchers tested whether blocking these chemokine pathways could enhance viral replication using a compound called TAK‑779, originally designed to inhibit chemokine signaling.

“When TAK‑779 was added to the HIE cultures, norovirus replication increased dramatically,” Kaur said. “We achieved replication for 10 to 15 consecutive passages,” indicating sustained viral growth.

“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.

Not all viral strains responded in the same way. TAK‑779 enhanced growth of strains GII.3, GII.17, and GI.1 but not the dominant outbreak strain GII.4. Corresponding author Mary K. Estes explained that GII.4 viruses do not induce the same chemokine response, suggesting another limiting mechanism. Her group continues optimizing HIE conditions to support these strains.