New Breakthrough Unlocks Continuous Norovirus Cultivation, Paving Way for Vaccines and Treatments

Researchers at Baylor College of Medicine have reported a significant breakthrough in human norovirus (HuNoV) research, overcoming a major limitation in continuous viral cultivation. Norovirus is a leading cause of acute viral gastroenteritis worldwide, with severe outcomes primarily among young children, the elderly, and immunocompromised individuals.

There are currently no approved vaccines or antiviral therapies, with management relying on supportive care.

Overcoming Previous Limitations

Previous research in 2016 allowed scientists to grow HuNoV in human intestinal enteroids (HIEs), also known as 'mini-guts.' However, this method prevented continuous replication, as the virus would stop growing after a few rounds. This limitation hindered the development of stable viral stocks and required reliance on limited and inconsistent patient stool samples for experiments.

Uncovering the Restriction Factor

To address this challenge, the research team investigated factors restricting viral replication. Using RNA sequencing, they discovered that infected HIEs produced high levels of specific chemokines—molecules involved in immune responses. These key chemokines identified were CXCL10, CXCL11, and CCL5.

A Drug-Enabled Solution

The team found that blocking the signaling of these chemokines with a drug called TAK 779 dramatically increased norovirus replication in HIE cultures. This intervention allowed the virus to spread throughout the cells, enabling 10 to 15 consecutive passages.

This achievement allows for the generation of consistent batches of infectious virus from lab cultures, a capability researchers have sought for decades.

Strain-Specific Responses

The study also noted that not all HuNoV strains responded identically to TAK 779. While it significantly enhanced the replication of GII.3, GII.17, and GI.1 strains, it did not improve growth for GII.4 strains, which are the most common cause of human outbreaks. This difference is attributed to GII.4 viruses not triggering the same chemokine secretion in HIEs, suggesting a different limiting process for their growth. Efforts are ongoing to optimize HIE culture conditions for GII.4 and other HuNoV strains.

Future Implications

This breakthrough represents a substantial advancement for norovirus research. It will facilitate comprehensive studies of viral structure, accelerate antiviral drug screening, and aid in vaccine development, even for laboratories without access to patient stool samples.